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Sacha Gnjatic

  • SENIOR FACULTY Medicine, Hematology and Medical Oncology
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Education

  • BSc3, University College London

  • MSc, Institut Pasteur

  • Undergraduate, Ecole Normale Supérieure

  • PhD, University Paris VII

  • Memorial Sloan-Kettering - Ludwig Institute

Biography

       Dr. Sacha Gnjatic received his PhD in Immunology from the University of Paris VII after completing a fellowship at the Institut Cochin in Paris. Following a post-doctoral fellowship in Lloyd J. Old’s laboratory at Memorial Sloan-Kettering (MSKCC) in New York, Dr. Gnjatic
 was appointed to the Ludwig Institute for Cancer Research
 at MSKCC, where he eventually became Associate Member, and was named Director of Immunological Monitoring at the Ludwig Center for Immunotherapy.
       In 2013, Dr. Gnjatic moved to Icahn School of Medicine at Mount Sinai, New York, where he was appointed as Associate Professor of Medicine at the Tisch Cancer Institute and Immunology Institute. In addition, he serves as Associate Director of the Human Immune Monitoring Center at Mount Sinai.
       Dr. Gnjatic focuses on human immune responses to cancer in an antigen-specific manner, to define new targets for the development of cancer immunotherapies, ask how these immunotherapies work and why they may fail. Areas of research include: Characterization of serological and cellular immune responses against tumor antigens such as MAGE-A3 or NY-ESO-1, spontaneously occurring or induced by cancer immunotherapy, using state-of-the-art T cell methods and large-scale seromic profiling; Mechanisms of antigen presentation to T cells, to evaluate viral, bacterial, and parasitic vectors, and cross-presentation of antigen to HLA; Impact of immunoregulation on tumor antigen-specific responses, from co-inhibitory molecules expressed on T cells at the tumor site to the effect of regulatory T cells and immune checkpoint blockade on anti-tumor effectors, with a recent emphasis on the role of immunosuppressive mechanisms in the tumor microenvironment. 
       Dr. Gnjatic’s research has established the immunological bases for evaluating human cancer vaccines in over 40 clinical trials. His work has resulted in more than 120 publications in high-impact peer-reviewed journals and nearly 10 patents.   

Research

Characterization of serological and cellular immune responses against tumor antigens:

Characterization of serological and cellular immune responses against tumor antigens such as p53, MAGE-A3, and NY-ESO-1, for their capacity to induce immune responses both spontaneously and in the setting of cancer immunotherapy. Pioneering large-scale seromic profiling to find biomarkers and new targets of tumor immunity.

Impact of immunoregulation on tumor antigen-specific responses:

Impact of immunoregulation on tumor antigen-specific responses, from co-inhibitory molecules expressed on T cells at the tumor site to the effect of regulatory T cells on anti-tumor effectors.

Mechanisms of antigen presentation to T cells:

Mechanisms of antigen presentation to T cells, including defining epitopes, evaluating viral, bacterial, and parasitic vectors, cross-presentation of antigen to HLA class I, and endogenous antigen presentation to HLA class II.

Publications

Sabado RL, Pavlick A, Gnjatic S, Cruz CM, Vengco I, Hasan F, Spadaccia M, Darvishian F, Chiriboga L, Holman RM, Escalon J, Muren C, Escano C, Yepes E, Sharpe D, Vasilakos JP, Rolnitzsky L, Goldberg JD, Mandeli J, Adams S, Jungbluth A, Pan L, Venhaus R, Ott PA, Bhardwaj N. Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma. Cancer immunology research 2015 Mar; 3(3).

Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buqué A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, Apte RN, Aranda F, Ayyoub M, Beckhove P, Blay JY, Bracci L, Caignard A, Castelli C, Cavallo F, Celis E, Cerundolo V, Clayton A, Colombo MP, Coussens L, Dhodapkar MV, Eggermont AM, Fearon DT, Fridman WH, Fučíková J, Gabrilovich DI, Galon J, Garg A, Ghiringhelli F, Giaccone G, Gilboa E, Gnjatic S, Hoos A, Hosmalin A, Jäger D, Kalinski P, Kärre K, Kepp O, Kiessling R, Kirkwood JM, Klein E, Knuth A, Lewis CE, Liblau R, Lotze MT, Lugli E, Mach JP, Mattei F, Mavilio D, Melero I, Melief CJ, Mittendorf EA, Moretta L, Odunsi A, Okada H, Palucka AK, Peter ME, Pienta KJ, Porgador A, Prendergast GC, Rabinovich GA, Restifo NP, Rizvi N, Sautès-Fridman C, Schreiber H, Seliger B, Shiku H, Silva-Santos B, Smyth MJ, Speiser DE, Spisek R, Srivastava PK, Talmadge JE, Tartour E, Van Der Burg SH, Van Den Eynde BJ, Vile R, Wagner H, Weber JS, Whiteside TL, Wolchok JD, Zitvogel L, Zou W, Kroemer G. Classification of current anticancer immunotherapies. Oncotarget 2014 Dec; 5(24).

Germain C, Gnjatic S, Dieu-Nosjean MC. Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity. Frontiers in immunology 2015; 6.

Parikh F, Duluc D, Imai N, Clark A, Misiukiewicz K, Bonomi M, Gupta V, Patsias A, Parides M, Demicco EG, Zhang DY, Kim-Schulze S, Kao J, Gnjatic S, Oh S, Posner MR, Sikora AG. Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer. Cancer research 2014 Dec; 74(24).

Alabanza L, Gnjatic S, Bhardwaj N, Brody J. Intratumoral checkpoint subversion as a strategy for minimizing adverse effects: Harvesting the power of TILs without harvesting TILs. Oncoimmunology 2014; 3.

Remark R, Becker C, Gomez JE, Damotte D, Dieu-Nosjean MC, Sautès-Fridman C, Fridman WH, Powell CA, Altorki NK, Merad M, Gnjatic S. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. American journal of respiratory and critical care medicine 2015 Feb; 191(4).

Daudi S, Eng KH, Mhawech-Fauceglia P, Morrison C, Miliotto A, Beck A, Matsuzaki J, Tsuji T, Groman A, Gnjatic S, Spagnoli G, Lele S, Odunsi K. Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer. PloS one 2014; 9(8).

Odunsi K, Matsuzaki J, James SR, Mhawech-Fauceglia P, Tsuji T, Miller A, Zhang W, Akers SN, Griffiths EA, Miliotto A, Beck A, Batt CA, Ritter G, Lele S, Gnjatic S, Karpf AR. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer immunology research 2014 Jan; 2(1).

Matsuzaki J, Tsuji T, Luescher I, Old LJ, Shrikant P, Gnjatic S, Odunsi K. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells. Cancer immunology research 2014 Apr; 2(4).

Tsuji T, Sabbatini P, Jungbluth AA, Ritter E, Pan L, Ritter G, Ferran L, Spriggs D, Salazar AM, Gnjatic S. Effect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial. Cancer immunology research 2013 Nov; 1(5).

Karbach J, Gnjatic S, Biskamp M, Atmaca A, Weidmann E, Brandt K, Wahle C, Bernhard H, Knuth A, Jäger E. Long-term complete remission following radiosurgery and immunotherapy in a melanoma patient with brain metastasis: immunologic correlates. Cancer immunology research 2014 May; 2(5).

Tyler EM, Jungbluth AA, Gnjatic S, O'Reilly RJ, Koehne G. Cancer-testis antigen 7 expression and immune responses following allogeneic stem cell transplantation for multiple myeloma. Cancer immunology research 2014 Jun; 2(6).

Germain C, Gnjatic S, Tamzalit F, Knockaert S, Remark R, Goc J, Lepelley A, Becht E, Katsahian S, Bizouard G, Validire P, Damotte D, Alifano M, Magdeleinat P, Cremer I, Teillaud JL, Fridman WH, Sautès-Fridman C, Dieu-Nosjean MC. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. American journal of respiratory and critical care medicine 2014 Apr; 189(7).

Chen JL, Dawoodji A, Tarlton A, Gnjatic S, Tajar A, Karydis I, Browning J, Pratap S, Verfaille C, Venhaus RR, Pan L, Altman DG, Cebon JS, Old LL, Nathan P, Ottensmeier C, Middleton M, Cerundolo V. NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus. International journal of cancer. Journal international du cancer 2015 Mar; 136(6).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Below are financial relationships with industry reported by Dr. Gnjatic during 2014 and/or 2015. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Scientific Advisory Board:

  • Boehringer Ingelheim Corporation

Royalty Payments:

  • GlaxoSmithKline

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.

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