Photo of Arlene H. Sharpe,  MD, PhD

Arlene H. Sharpe, MD, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-6568
Fax: (617) 432-6570


Arlene_sharpe@hms.harvard.edu

Arlene H. Sharpe, MD, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • George Fabyan Professor of Comparative Pathology, Microbiology and Immunobiology, Harvard Medical School
  • Vice Chair for Education, Pathology, Harvard Medical School
  • Co-Director, HITI, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council

Research Abstract

Dr. Sharpe's research is focused on understanding the role of costimulatory molecules in T cell activation in vivo. Learning how to manipulate costimulatory pathways may provide new therapeutic approaches for augmenting immunity to microbes and tumor antigens, as well as for inhibiting immune responses to prevent graft rejection and treat autoimmune diseases. The approach that her laboratory has taken is to focus on the obligatory in vivo functions of costimulatory molecules by using targeted gene disruption to generate mouse strains lacking T cell costimulatory molecules. Analysis of the key costimulatory pathway involving B7 costimulatory molecules and their receptors, CD28 and CTLA-4, has been her major focus. Her laboratory is investigating the role of B7-1 and B7-2 in T cell activation, T cell tolerance, and autoimmune responses. By examining what factors elicit residual immune responses in mice lacking both B7 costimulators, her laboratory is also examining the role of additional costimulatory pathways in T cell activation. The laboratory is studying interactions between costimulatory pathways and the hierarchy of costimulatory pathways throughout the generation and analysis of mice lacking other costimulatory molecules (including CD48, OX40 ligand, CD40 ligand and SLAM). A second project focuses on analyzing the critical negative regulatory role of CTLA-4 in T cell activation and tolerance. The third project is directed at defining the molecular basis for the highly regulated expression of B7 costimulatory molecules. Because genetic mapping studies have identified the chromosomal regions containing CD28/CTLA-4 and B7/B7-2 loci as important for the development of IDDM and EAE, the laboratory is also examining whether polymorphisms within these genes lead to altered expression or protein function in autoimmune prone mouse strains, thereby contributing the pathogenesis of autoimmunity.

Publications from Harvard Catalyst Profiles

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  • Kuchroo JR, Hafler DA, Sharpe AH, Lucca LE. The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity. Sci Immunol 2021; 6:eabf4034. PubMed
  • Bu X, Juneja VR, Reynolds CG, Mahoney KM, Bu MT, McGuire KA, Maleri S, Hua P, Zhu B, Klein SR, Greenfield EA, Armand P, Ritz J, Sharpe AH, Freeman GJ. Monitoring PD-1 Phosphorylation to Evaluate PD-1 Signaling during Antitumor Immune Responses. Cancer Immunol Res 2021. PubMed
  • Pelka K, Hofree M, Chen JH, Sarkizova S, Pirl JD, Jorgji V, Bejnood A, Dionne D, Ge WH, Xu KH, Chao SX, Zollinger DR, Lieb DJ, Reeves JW, Fuhrman CA, Hoang ML, Delorey T, Nguyen LT, Waldman J, Klapholz M, Wakiro I, Cohen O, Albers J, Smillie CS, Cuoco MS, Wu J, Su MJ, Yeung J, Vijaykumar B, Magnuson AM, Asinovski N, Moll T, Goder-Reiser MN, Applebaum AS, Brais LK, DelloStritto LK, Denning SL, Phillips ST, Hill EK, Meehan JK, Frederick DT, Sharova T, Kanodia A, Todres EZ, Jané-Valbuena J, Biton M, Izar B, Lambden CD, Clancy TE, Bleday R, Melnitchouk N, Irani J, Kunitake H, Berger DL, Srivastava A, Hornick JL, Ogino S, Rotem A, Vigneau S, Johnson BE, Corcoran RB, Sharpe AH, Kuchroo VK, Ng K, Giannakis M, Nieman LT, Boland GM, Aguirre AJ, Anderson AC, Rozenblatt-Rosen O, Regev A, Hacohen N. Spatially organized multicellular immune hubs in human colorectal cancer. Cell 2021; 184:4734-4752.e20. PubMed
  • Evavold CL, Hafner-Bratkovič I, Devant P, D'Andrea JM, Ngwa EM, Boršić E, Doench JG, LaFleur MW, Sharpe AH, Thiagarajah JR, Kagan JC. Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell 2021. PubMed
  • Collier JL, Weiss SA, Pauken KE, Sen DR, Sharpe AH. Not-so-opposite ends of the spectrum: CD8 T cell dysfunction across chronic infection, cancer and autoimmunity. Nat Immunol 2021; 22:809-819. PubMed
  • Pauken KE, Torchia JA, Chaudhri A, Sharpe AH, Freeman GJ. Emerging concepts in PD-1 checkpoint biology. Semin Immunol 2021. PubMed
  • Braun DA, Street K, Burke KP, Cookmeyer DL, Denize T, Pedersen CB, Gohil SH, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin DB, Steinharter J, Bouchard G, Sun M, Pimenta EM, Xu W, Mahoney KM, McGregor BA, Hirsch MS, Chang SL, Livak KJ, McDermott DF, Shukla SA, Olsen LR, Signoretti S, Sharpe AH, Irizarry RA, Choueiri TK, Wu CJ. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021; 39:632-648.e8. PubMed
  • Pauken KE, Shahid O, Lagattuta KA, Mahuron KM, Luber JM, Lowe MM, Huang L, Delaney C, Long JM, Fung ME, Newcomer K, Tsai KK, Chow M, Guinn S, Kuchroo JR, Burke KP, Schenkel JM, Rosenblum MD, Daud AI, Sharpe AH, Singer M. Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment. J Exp Med 2021. PubMed
  • Moslehi J, Lichtman AH, Sharpe AH, Galluzzi L, Kitsis RN. Immune checkpoint inhibitor-associated myocarditis: manifestations and mechanisms. J Clin Invest 2021. PubMed
  • Lo JA, Kawakubo M, Juneja VR, Su MY, Erlich TH, LaFleur MW, Kemeny LV, Rashid M, Malehmir M, Rabi SA, Raghavan R, Allouche J, Kasumova G, Frederick DT, Pauken KE, Weng QY, Pereira da Silva M, Xu Y, van der Sande AAJ, Silkworth W, Roider E, Browne EP, Lieb DJ, Wang B, Garraway LA, Wu CJ, Flaherty KT, Brinckerhoff CE, Mullins DW, Adams DJ, Hacohen N, Hoang MP, Boland GM, Freeman GJ, Sharpe AH, Manstein D, Fisher DE. Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses. Sci Transl Med 2021. PubMed
  • Drijvers JM, Gillis JE, Muijlwijk T, Nguyen TH, Gaudiano EF, Harris IS, LaFleur MW, Ringel AE, Yao CH, Kurmi K, Juneja VR, Trombley JD, Haigis MC, Sharpe AH. Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8 T Cells. Cancer Immunol Res 2021; 9:184-199. PubMed
  • Johnnidis JB, Muroyama Y, Ngiow SF, Chen Z, Manne S, Cai Z, Song S, Platt JM, Schenkel JM, Abdel-Hakeem M, Beltra JC, Greenplate AR, Ali MA, Nzingha K, Giles JR, Harly C, Attanasio J, Pauken KE, Bengsch B, Paley MA, Tomov VT, Kurachi M, Vignali DAA, Sharpe AH, Reiner SL, Bhandoola A, Johnson FB, Wherry EJ. Inhibitory signaling sustains a distinct early memory CD8 T cell precursor that is resistant to DNA damage. Sci Immunol 2021. PubMed
  • Tan CL, Kuchroo JR, Sage PT, Liang D, Francisco LM, Buck J, Thaker YR, Zhang Q, McArdel SL, Juneja VR, Lee SJ, Lovitch SB, Lian C, Murphy GF, Blazar BR, Vignali DAA, Freeman GJ, Sharpe AH. PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance. J Exp Med 2021. PubMed
  • Burke KP, Grebinoski S, Sharpe AH, Vignali DAA. Understanding adverse events of immunotherapy: A mechanistic perspective. J Exp Med 2021. PubMed
  • Andrews LP, Vignali KM, Szymczak-Workman AL, Burton AR, Brunazzi EA, Ngiow SF, Harusato A, Sharpe AH, Wherry EJ, Taniuchi I, Workman CJ, Vignali DAA. A Cre-driven allele-conditioning line to interrogate CD4 conventional T cells. Immunity 2021; 54:2209-2217.e6. PubMed
  • Howard E, Hurrell BP, Helou DG, Quach C, Painter JD, Shafiei-Jahani P, Fung M, Gill PS, Soroosh P, Sharpe AH, Akbari O. PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma. 2021; 12:733136. PubMed
  • Schneider JL, Rowe JH, Garcia-de-Alba C, Kim CF, Sharpe AH, Haigis MC. The aging lung: Physiology, disease, and immunity. Cell 2021; 184:1990-2019. PubMed
  • Bayless NL, Bluestone JA, Bucktrout S, Butterfield LH, Jaffee EM, Koch CA, Roep BO, Sharpe AH, Murphy WJ, Villani AC, Walunas TL. Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR. J Immunother Cancer 2021. PubMed
  • Ringel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, Yao CH, Yoon H, Sage PT, LaFleur MW, Trombley JD, Jacobson CA, Maliga Z, Gygi SP, Sorger PK, Rabinowitz JD, Sharpe AH, Haigis MC. Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity. Cell 2020; 183:1848-1866.e26. PubMed
  • Sungnak W, Wagner A, Kowalczyk MS, Bod L, Kye YC, Sage PT, Sharpe AH, Sobel RA, Quintana FJ, Rozenblatt-Rosen O, Regev A, Wang C, Yosef N, Kuchroo VK. T Follicular Regulatory Cell-Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity. J Immunol 2020; 205:3247-3262. PubMed
  • Ficial M, Jegede OA, Sant'Angelo M, Hou Y, Flaifel A, Pignon JC, Braun DA, Wind-Rotolo M, Sticco-Ivins MA, Catalano PJ, Freeman GJ, Sharpe AH, Hodi FS, Motzer RJ, Wu CJ, Atkins MB, McDermott DF, Shukla SA, Choueiri TK, Signoretti S. Expression of T-Cell Exhaustion Molecules and Human Endogenous Retroviruses as Predictive Biomarkers for Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma. Clin Cancer Res 2020. PubMed
  • Chen IX, Newcomer K, Pauken KE, Juneja VR, Naxerova K, Wu MW, Pinter M, Sen DR, Singer M, Sharpe AH, Jain RK. A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. Proc Natl Acad Sci U S A 2020; 117:23684-23694. PubMed
  • Pauken KE, Godec J, Odorizzi PM, Brown KE, Yates KB, Ngiow SF, Burke KP, Maleri S, Grande SM, Francisco LM, Ali MA, Imam S, Freeman GJ, Haining WN, Wherry EJ, Sharpe AH. The PD-1 Pathway Regulates Development and Function of Memory CD8 T Cells following Respiratory Viral Infection. Cell Rep 2020; 31:107827. PubMed
  • Braun DA, Hou Y, Bakouny Z, Ficial M, Sant' Angelo M, Forman J, Ross-Macdonald P, Berger AC, Jegede OA, Elagina L, Steinharter J, Sun M, Wind-Rotolo M, Pignon JC, Cherniack AD, Lichtenstein L, Neuberg D, Catalano P, Freeman GJ, Sharpe AH, McDermott DF, Van Allen EM, Signoretti S, Wu CJ, Shukla SA, Choueiri TK. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat Med 2020; 26:909-918. PubMed
  • Sage PT, Sharpe AH. The multifaceted functions of follicular regulatory T cells. Curr Opin Immunol 2020; 67:68-74. PubMed
  • Drijvers JM, Sharpe AH, Haigis MC. The effects of age and systemic metabolism on anti-tumor T cell responses. Elife 2020. PubMed
  • LaFleur MW, Miller BC, Sharpe AH. Prevention of CAR-T-cell dysfunction. Nat Biomed Eng 2020; 4:16-17. PubMed
  • Brown FD, Sen DR, LaFleur MW, Godec J, Lukacs-Kornek V, Schildberg FA, Kim HJ, Yates KB, Ricoult SJH, Bi K, Trombley JD, Kapoor VN, Stanley IA, Cremasco V, Danial NN, Manning BD, Sharpe AH, Haining WN, Turley SJ. Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling. Nat Immunol 2019; 20:1668-1680. PubMed
  • Clement RL, Daccache J, Mohammed MT, Diallo A, Blazar BR, Kuchroo VK, Lovitch SB, Sharpe AH, Sage PT. Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses. Nat Immunol 2019; 20:1360-1371. PubMed
  • LaFleur MW, Nguyen TH, Coxe MA, Miller BC, Yates KB, Gillis JE, Sen DR, Gaudiano EF, Al Abosy R, Freeman GJ, Haining WN, Sharpe AH. PTPN2 regulates the generation of exhausted CD8 T cell subpopulations and restrains tumor immunity. Nat Immunol 2019; 20:1335-1347. PubMed
  • Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, Schietinger A, Schumacher TN, Schwartzberg PL, Sharpe AH, Speiser DE, Wherry EJ, Youngblood BA, Zehn D. Defining 'T cell exhaustion'. Nat Rev Immunol 2019. PubMed
  • Ron-Harel N, Ghergurovich JM, Notarangelo G, LaFleur MW, Tsubosaka Y, Sharpe AH, Rabinowitz JD, Haigis MC. T Cell Activation Depends on Extracellular Alanine. Cell Rep 2019; 28:3011-3021.e4. PubMed
  • Rashidian M, LaFleur MW, Verschoor VL, Dongre A, Zhang Y, Nguyen TH, Kolifrath S, Aref AR, Lau CJ, Paweletz CP, Bu X, Freeman GJ, Barrasa MI, Weinberg RA, Sharpe AH, Ploegh HL. Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade. Proc Natl Acad Sci U S A 2019; 116:16971-16980. PubMed
  • Pauken KE, Dougan M, Rose NR, Lichtman AH, Sharpe AH. Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities. Trends Immunol 2019; 40:511-523. PubMed
  • Pignon JC, Jegede O, Shukla SA, Braun DA, Horak CE, Wind-Rotolo M, Ishii Y, Catalano PJ, Grosha J, Flaifel A, Novak JS, Mahoney KM, Freeman GJ, Sharpe AH, Hodi FS, Motzer RJ, Choueiri TK, Wu CJ, Atkins MB, McDermott DF, Signoretti S. irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial. Clin Cancer Res 2019; 25:2174-2184. PubMed
  • Hou S, Clement RL, Diallo A, Blazar BR, Rudensky AY, Sharpe AH, Sage PT. FoxP3 and Ezh2 regulate Tfr cell suppressive function and transcriptional program. J Exp Med 2019; 216:605-620. PubMed
  • Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, Yates KB, Lako A, Felt K, Naik GS, Manos M, Gjini E, Kuchroo JR, Ishizuka JJ, Collier JL, Griffin GK, Maleri S, Comstock DE, Weiss SA, Brown FD, Panda A, Zimmer MD, Manguso RT, Hodi FS, Rodig SJ, Sharpe AH, Haining WN. Subsets of exhausted CD8 T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol 2019; 20:326-336. PubMed
  • Paz K, Flynn R, Du J, Tannheimer S, Johnson AJ, Dong S, Stark AK, Okkenhaug K, Panoskaltsis-Mortari A, Sage PT, Sharpe AH, Luznik L, Ritz J, Soiffer RJ, Cutler CS, Koreth J, Antin JH, Miklos DB, MacDonald KP, Hill GR, Maillard I, Serody JS, Murphy WJ, Munn DH, Feser C, Zaiken M, Vanhaesebroeck B, Turka LA, Byrd JC, Blazar BR. Targeting PI3Kδ function for amelioration of murine chronic graft-versus-host disease. Am J Transplant 2019. PubMed
  • LaFleur MW, Nguyen TH, Coxe MA, Yates KB, Trombley JD, Weiss SA, Brown FD, Gillis JE, Coxe DJ, Doench JG, Haining WN, Sharpe AH. A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system. Nat Commun 2019; 10:1668. PubMed
  • Ron-Harel N, Notarangelo G, Ghergurovich JM, Paulo JA, Sage PT, Santos D, Satterstrom FK, Gygi SP, Rabinowitz JD, Sharpe AH, Haigis MC. Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice. Proc Natl Acad Sci U S A 2018; 115:13347-13352. PubMed
  • Paz K, Flynn R, Du J, Qi J, Luznik L, Maillard I, MacDonald KP, Hill GR, Serody JS, Murphy WJ, Sage PT, Sharpe AH, Miklos D, Culter CS, Koreth J, Antin JH, Soiffer RJ, Ritz J, Bradner JE, Melnick AM, Blazar B. Small-molecule BCL6 inhibitor effectively treats mice with non-sclerodermatous chronic graft-versus-host disease. Blood 2018. PubMed
  • Sheng W, LaFleur MW, Nguyen TH, Chen S, Chakravarthy A, Conway JR, Li Y, Chen H, Yang H, Hsu PH, Van Allen EM, Freeman GJ, De Carvalho DD, He HH, Sharpe AH, Shi Y. LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade. Cell 2018. PubMed
  • Ahn E, Araki K, Hashimoto M, Li W, Riley JL, Cheung J, Sharpe AH, Freeman GJ, Irving BA, Ahmed R. Role of PD-1 during effector CD8 T cell differentiation. Proc Natl Acad Sci U S A 2018; 115:4749-4754. PubMed
  • Yim SH, Everley RA, Schildberg FA, Lee SG, Orsi A, Barbati ZR, Karatepe K, Fomenko DE, Tsuji PA, Luo HR, Gygi SP, Sitia R, Sharpe AH, Hatfield DL, Gladyshev VN. Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. Cell Rep 2018; 23:1387-1398. PubMed
  • Liu HJ, Lizotte PH, Du H, Speranza MC, Lam HC, Vaughan S, Alesi N, Wong KK, Freeman GJ, Sharpe AH, Henske EP. TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti-PD-1/anti-CTLA-4 immunotherapy. JCI Insight 2018. PubMed
  • Sage PT, Schildberg FA, Sobel RA, Kuchroo VK, Freeman GJ, Sharpe AH. Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function. J Immunol 2018. PubMed
  • LaFleur MW, Muroyama Y, Drake CG, Sharpe AH. Inhibitors of the PD-1 Pathway in Tumor Therapy. J Immunol 2018; 200:375-383. PubMed
  • Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, Demetris AJ, Shlomchik MJ, Shlomchik WD. PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease. J Immunol 2018; 200:834-846. PubMed
  • Mooradian MJ, Reuben A, Prieto PA, Hazar-Rethinam M, Frederick DT, Nadres B, Piris A, Juneja V, Cooper ZA, Sharpe AH, Corcoran RB, Flaherty KT, Lawrence DP, Wargo JA, Sullivan RJ. A phase II study of combined therapy with a BRAF inhibitor (vemurafenib) and interleukin-2 (aldesleukin) in patients with metastatic melanoma. Oncoimmunology 2018; 7:e1423172. PubMed
  • Zhang R, Sage PT, Finn K, Huynh A, Blazar BR, Marangoni F, Mempel TR, Sharpe AH, Turka LA. B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells. J Immunol 2017; 199:3972-3980. PubMed
  • Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 2017. PubMed
  • Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB, Miller BC, Collins NB, Bi K, LaFleur MW, Juneja VR, Weiss SA, Lo J, Fisher DE, Miao D, Van Allen E, Root DE, Sharpe AH, Doench JG, Haining WN. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 2017; 547:413-418. PubMed
  • Moffett HF, Cartwright ANR, Kim HJ, Godec J, Pyrdol J, Äijö T, Martinez GJ, Rao A, Lu J, Golub TR, Cantor H, Sharpe AH, Novina CD, Wucherpfennig KW. The microRNA miR-31 inhibits CD8(+) T cell function in chronic viral infection. Nat Immunol 2017; 18:791-799. PubMed
  • Juneja VR, McGuire KA, Manguso RT, LaFleur MW, Collins N, Haining WN, Freeman GJ, Sharpe AH. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med 2017; 214:895-904. PubMed
  • Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, Konieczny BT, Daugherty CZ, Koenig L, Yu K, Sica GL, Sharpe AH, Freeman GJ, Blazar BR, Turka LA, Owonikoko TK, Pillai RN, Ramalingam SS, Araki K, Ahmed R. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 2017; 355:1423-1427. PubMed
  • Sharpe AH. Introduction to checkpoint inhibitors and cancer immunotherapy. Immunol Rev 2017; 276:5-8. PubMed
  • Sage PT, Ron-Harel N, Juneja VR, Sen DR, Maleri S, Sungnak W, Kuchroo VK, Haining WN, Chevrier N, Haigis M, Sharpe AH. Suppression by TFR cells leads to durable and selective inhibition of B cell effector function. Nat Immunol 2016. PubMed
  • McArdel SL, Brown DR, Sobel RA, Sharpe AH. Anti-CD48 Monoclonal Antibody Attenuates Experimental Autoimmune Encephalomyelitis by Limiting the Number of Pathogenic CD4+ T Cells. J Immunol 2016. PubMed
  • Karunarathne DS, Horne-Debets JM, Huang JX, Faleiro R, Leow CY, Amante F, Watkins TS, Miles JJ, Dwyer PJ, Stacey KJ, Yarski M, Poh CM, Lee JS, Cooper MA, Rénia L, Richard D, McCarthy JS, Sharpe AH, Wykes MN. Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4(+) T Cell Immunity. Immunity 2016; 45:333-45. PubMed
  • Im SJ, Hashimoto M, Gerner MY, Lee J, Kissick HT, Burger MC, Shan Q, Hale JS, Lee J, Nasti TH, Sharpe AH, Freeman GJ, Germain RN, Nakaya HI, Xue HH, Ahmed R. Defining CD8(+) T cells that provide the proliferative burst after PD-1 therapy. Nature 2016; 537:417-421. PubMed
  • Ron-Harel N, Santos D, Ghergurovich JM, Sage PT, Reddy A, Lovitch SB, Dephoure N, Satterstrom FK, Sheffer M, Spinelli JB, Gygi S, Rabinowitz JD, Sharpe AH, Haigis MC. Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation. Cell Metab 2016; 24:104-17. PubMed
  • Saha A, O'Connor RS, Thangavelu G, Lovitch SB, Dandamudi DB, Wilson CB, Vincent BG, Tkachev V, Pawlicki JM, Furlan SN, Kean LS, Aoyama K, Taylor PA, Panoskaltsis-Mortari A, Foncea R, Ranganathan P, Devine SM, Burrill JS, Guo L, Sacristan C, Snyder NW, Blair IA, Milone MC, Dustin ML, Riley JL, Bernlohr DA, Murphy WJ, Fife BT, Munn DH, Miller JS, Serody JS, Freeman GJ, Sharpe AH, Turka LA, Blazar BR. Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality. J Clin Invest 2016; 126:2642-60. PubMed
  • Chen PL, Roh W, Reuben A, Cooper ZA, Spencer CN, Prieto PA, Miller JP, Bassett RL, Gopalakrishnan V, Wani K, Petaccia De Macedo M, Austin-Breneman JL, Jiang H, Chang Q, Reddy SM, Chen WS, Tetzlaff MT, Broaddus RJ, Davies MA, Gershenwald JE, Haydu L, Lazar AJ, Patel SP, Hwu P, Hwu WJ, Diab A, Glitza IC, Woodman SE, Vence LM, Wistuba II, Amaria RN, Kwong LN, Prieto V, Davis RE, Ma W, Overwijk WW, Sharpe AH, Hu J, Futreal PA, Blando J, Sharma P, Allison JP, Chin L, Wargo JA. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. 2016. PubMed
  • Sakai S, Kauffman KD, Sallin MA, Sharpe AH, Young HA, Ganusov VV, Barber DL. CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease. PLoS Pathog. 2016; 12:e1005667. PubMed
  • Cooper ZA, Reuben A, Spencer CN, Prieto PA, Austin-Breneman JL, Jiang H, Haymaker C, Gopalakrishnan V, Tetzlaff MT, Frederick DT, Sullivan RJ, Amaria RN, Patel SP, Hwu P, Woodman SE, Glitza IC, Diab A, Vence LM, Rodriguez-Canales J, Parra ER, Wistuba II, Coussens LM, Sharpe AH, Flaherty KT, Gershenwald JE, Chin L, Davies MA, Clise-Dwyer K, Allison JP, Sharma P, Wargo JA. Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma. Oncoimmunology 2016; 5:e1136044. PubMed
  • Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory Pathways in Immunotherapy for Cancer. Annu Rev Immunol 2016. PubMed
  • Dobbins J, Gagnon E, Godec J, Pyrdol J, Vignali DA, Sharpe AH, Wucherpfennig KW. Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling. Sci Signal 2016; 9:ra75. PubMed
  • Mahoney KM, Sun H, Liao X, Hua P, Callea M, Greenfield EA, Hodi FS, Sharpe AH, Signoretti S, Rodig SJ, Freeman GJ. PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells. Cancer Immunol Res 2015; 3:1308-15. PubMed
  • Reardon DA, Gokhale PC, Klein SR, Ligon KL, Rodig SJ, Ramkissoon SH, Jones KL, Conway AS, Liao X, Zhou J, Wen PY, Van Den Abbeele AD, Hodi FS, Qin L, Kohl NE, Sharpe AH, Dranoff G, Freeman GJ. Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model. Cancer Immunol Res 2015. PubMed
  • Sharma MD, Shinde R, McGaha TL, Huang L, Holmgaard RB, Wolchok JD, Mautino MR, Celis E, Sharpe AH, Francisco LM, Powell JD, Yagita H, Mellor AL, Blazar BR, Munn DH. The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Sci Adv 2015; 1:e1500845. PubMed
  • Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, Cosgrove C, Ledderose C, Junger WG, Robson SC, Wherry EJ, Alter G, Goulder PJ, Klenerman P, Sharpe AH, Lauer GM, Haining WN. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog. 2015; 11:e1005177. PubMed
  • Paterson AM, Lovitch SB, Sage PT, Juneja VR, Lee Y, Trombley JD, Arancibia-Cárcamo CV, Sobel RA, Rudensky AY, Kuchroo VK, Freeman GJ, Sharpe AH. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med 2015; 212:1603-21. PubMed
  • Kleffel S, Posch C, Barthel SR, Mueller H, Schlapbach C, Guenova E, Elco CP, Lee N, Juneja VR, Zhan Q, Lian CG, Thomi R, Hoetzenecker W, Cozzio A, Dummer R, Mihm MC, Flaherty KT, Frank MH, Murphy GF, Sharpe AH, Kupper TS, Schatton T. Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell 2015; 162:1242-56. PubMed
  • Schatton T, Yang J, Kleffel S, Uehara M, Barthel SR, Schlapbach C, Zhan Q, Dudeney S, Mueller H, Lee N, de Vries JC, Meier B, Vander Beken S, Kluth MA, Ganss C, Sharpe AH, Waaga-Gasser AM, Sayegh MH, Abdi R, Scharffetter-Kochanek K, Murphy GF, Kupper TS, Frank NY, Frank MH. ABCB5 Identifies Immunoregulatory Dermal Cells. Cell Rep 2015. PubMed
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  • Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber WJ, Mulder GE, Toebes M, Vesely MD, Lam SS, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee HG, Melief CJ, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014; 515:577-81. PubMed
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  • Cooper ZA, Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, Lo JA, Hodi FS, Freeman GJ, Bosenberg MW, McMahon M, Flaherty KT, Fisher DE, Sharpe AH, Wargo JA. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res 2014. PubMed
  • Xiao Y, Yu S, Zhu B, Bedoret D, Bu X, Francisco LM, Hua P, Duke-Cohan JS, Umetsu DT, Sharpe AH, DeKruyff RH, Freeman GJ. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 2014. PubMed
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  • Mott KR, Allen SJ, Zandian M, Akbari O, Hamrah P, Maazi H, Wechsler SL, Sharpe AH, Freeman GJ, Ghiasi H. Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses. PLoS ONE 2014; 9:e87617. PubMed
  • Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, Munn DH, Murphy WJ, Azuma M, Yagita H, Fife BT, Sayegh MH, Najafian N, Socie G, Ahmed R, Freeman GJ, Sharpe AH, Blazar BR. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood 2013; 122:3062-73. PubMed
  • Cooper ZA, Frederick DT, Juneja VR, Sullivan RJ, Lawrence DP, Piris A, Sharpe AH, Fisher DE, Flaherty KT, Wargo JA. BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes. Oncoimmunology 2013; 2:e26615. PubMed
  • Fuller MJ, Callendret B, Zhu B, Freeman GJ, Hasselschwert DL, Satterfield W, Sharpe AH, Dustin LB, Rice CM, Grakoui A, Ahmed R, Walker CM. Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1). Proc Natl Acad Sci U S A 2013; 110:15001-6. PubMed
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  • Sage PT, Francisco LM, Carman CV, Sharpe AH. The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nat Immunol 2013; 14:152-61. PubMed
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  • Sham CW, Chan AM, Kwong JM, Caprioli J, Nusinowitz S, Chen B, Lee JG, Gandhi NM, Francisco LM, Sharpe AH, Chen L, Braun J, Gordon LK. Neuronal programmed cell death-1 ligand expression regulates retinal ganglion cell number in neonatal and adult mice. J Neuroophthalmol 2012; 32:227-37. PubMed
  • Silberman D, Bucknum A, Bartlett T, Composto G, Kozlowski M, Walker A, Werda A, Cua J, Sharpe AH, Somerville JE, Riggs JE. CD28 ligation increases macrophage suppression of T-cell proliferation. Cell Mol Immunol 2012; 9:341-9. PubMed
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  • Bu DX, Tarrio M, Maganto-Garcia E, Stavrakis G, Tajima G, Lederer J, Jarolim P, Freeman GJ, Sharpe AH, Lichtman AH. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol 2011. PubMed
  • Jin Y, Chauhan SK, El Annan J, Annan JE, Sage PT, Sharpe AH, Dana R. A novel function for programmed death ligand-1 regulation of angiogenesis. Am J Pathol 2011; 178:1922-9. PubMed
  • Barber DL, Mayer-Barber KD, Feng CG, Sharpe AH, Sher A. CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol 2011; 186:1598-607. PubMed
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  • Ruffner MA, Kim SH, Bianco NR, Francisco LM, Sharpe AH, Robbins PD. B7-1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC and DC-derived exosomes for in vivo function. Eur J Immunol 2009; 39:3084-90. PubMed
  • Chen L,Sham CW,Chan AM,Francisco LM,Wu Y,Mareninov S,Sharpe AH,Freeman G,Yang XJ,Braun J,Gordon LK. Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells. Invest Ophthalmol Vis Sci 2009; 50:4941-8. PubMed
  • Pot C, Jin H, Awasthi A, Liu SM, Lai CY, Madan R, Sharpe AH, Karp CL, Miaw SC, Ho IC, Kuchroo VK. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol 2009; 183:797-801. PubMed
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  • Reynoso ED,Elpek KG,Francisco L,Bronson R,Bellemare-Pelletier A,Sharpe AH,Freeman GJ,Turley SJ. Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade. J Immunol 2009; 182:2102-12. PubMed
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  • Schmidt EM,Wang CJ,Ryan GA,Clough LE,Qureshi OS,Goodall M,Abbas AK,Sharpe AH,Sansom DM,Walker LS. Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. J Immunol 2009; 182:274-82. PubMed
  • Chen L,Pai V,Levinson R,Sharpe AH,Freeman GJ,Braun J,Gordon LK. Constitutive neuronal expression of the immune regulator, programmed death 1 (PD-1), identified during experimental autoimmune uveitis. Ocul Immunol Inflamm 2009; 17:47-55. PubMed
  • Brooks DG,Ha SJ,Elsaesser H,Sharpe AH,Freeman GJ,Oldstone MB. IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection. Proc Natl Acad Sci U S A 2008; 105:20428-33. PubMed
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  • Taylor PA,Ehrhardt MJ,Lees CJ,Panoskaltsis-Mortari A,Krieg AM,Sharpe AH,Murphy WJ,Serody JS,Hemmi H,Akira S,Levy RB,Blazar BR. TLR agonists regulate alloresponses and uncover a critical role for donor APCs in allogeneic bone marrow rejection. Blood 2008; 112:3508-16. PubMed
  • Duan B,Niu H,Xu Z,Sharpe AH,Croker BP,Sobel ES,Morel L. Intrafollicular location of marginal zone/CD1d(hi) B cells is associated with autoimmune pathology in a mouse model of lupus. Lab Invest 2008; 88:1008-20. PubMed
  • Lucas JA,Menke J,Rabacal WA,Schoen FJ,Sharpe AH,Kelley VR. Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice. J Immunol 2008; 181:2513-21. PubMed
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  • Kobayashi N, Karisola P, Peña-Cruz V, Dorfman DM, Jinushi M, Umetsu SE, Butte MJ, Nagumo H, Chernova I, Zhu B, Sharpe AH, Ito S, Dranoff G, Kaplan GG, Casasnovas JM, Umetsu DT, Dekruyff RH, Freeman GJ. TIM-1 and TIM-4 Glycoproteins Bind Phosphatidylserine and Mediate Uptake of Apoptotic Cells. Immunity 2007; 27:927-40. PubMed
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  • Shen L, Jin Y, Freeman GJ, Sharpe AH, Dana MR. The function of donor versus recipient programmed death-ligand 1 in corneal allograft survival. J Immunol 2007; 179:3672-9. PubMed
  • Tai X, Van Laethem F, Sharpe AH, Singer A. Induction of autoimmune disease in CTLA-4-/- mice depends on a specific CD28 motif that is required for in vivo costimulation. Proc Natl Acad Sci U S A 2007; 104:13756-61. PubMed
  • Love VA, Grabie N, Duramad P, Stavrakis G, Sharpe A, Lichtman A. CTLA-4 ablation and interleukin-12 driven differentiation synergistically augment cardiac pathogenicity of cytotoxic T lymphocytes. Circ Res 2007; 101:248-57. PubMed
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  • Lerner SP, Bajorin DF, Dinney CP, Efstathiou JA, Groshen S, Hahn NM, Hansel D, Kwiatkowski D, O'Donnell M, Rosenberg J, Svatek R, Abrams JS, Al-Ahmadie H, Apolo AB, Bellmunt J, Callahan M, Cha EK, Drake C, Jarow J, Kamat A, Kim W, Knowles M, Mann B, Marchionni L, McConkey D, McShane L, Ramirez N, Sharabi A, Sharpe AH, Solit D, Tangen CM, Amiri AT, Van Allen E, West PJ, Witjes JA, Quale DZ. Summary and Recommendations from the National Cancer Institute's Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer. Bl Cancer ; 2:165-202. PubMed
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