Dr. Yaron Carmi

Senior Lecturer, Department of Pathology, Sackler Faculty of Medicine

Cellular and Molecular Mechanisms of Antigen-Restricted Rumor Immunity

The goal of our work is to provide a detailed understanding of the mechanisms, signals and molecular pathways that regulate discriminating self from non-self and give rise to tumor-specific cytotoxic T cell immunity. Our specific aims are to address the following: 1) What are the cellular and molecular elements that enable the immune system to recognize subtle antigenic variations from self to initiate a cytotoxic immune response? 2) How is the specificity of the induced immune response determined? In other words, what is the process by which the presentation of diverse antigens by DC is reduced to activation of specific effector T cells? Understanding the means by which DC and T cells communicate to initiate antigen-restricted tumor immunity and how these processes are regulated will provide a roadmap for designing novel, more potent cancer immunotherapies.

Santana-Magal N., Rasoulouniriana D., Vladimirsky J., Rider P., Carmi Y. 2017. Isolation of monocyte-derived dendritic cells and their activation with tumor immune complexs. 2017. JoVE. In press.

Spitzer MH*, Y. Carmi Y*, NE. Reticker-Flynn NE*, D. Madhireddy D, PF. Gherardini PF, J. Chabon J, GP. Nolan GP and EG. Engleman EG. Modeling effective cancer immunotherapy reveals the importance of systemic immunity. 2017, Cell 168, 487–502. *co-equal contribution

Zhang H, Gregorio JD, Iwahori T, Zhang X, Choi O. Tolentino LL, Prestwood T, Carmi Y, Engleman EG. A novel subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. 2017, Proc Natl Acad Sci USA. 114:1988-1993.

Bhattacharya N, Yuan R, Prestwood TR, Hweixian Leong P, DiMaio MA, Pham TD, Carmi Y, Kenkel JA, Hulett R, Wang J, Winer D, Napoli JL, Engleman EG. Retinoic acid drives anti-tumor CD8+ T cell immunity in colorectal cancer. 2016. Immunity.

Carmi Y, Prestwood TR, Spitzer MH, Linde IL, Chabon J, Reticker-Flynn NE, Bhattacharya N, Zhang H, Zhang X, Basto PA, Burt BM, Alonso MN, Engleman EG. Akt and SHP1 are dendritic cell-intrinsic checkpoints for tumor immunity. J Clin Invest Insight. 2016. 

Rider P, Carmi Y, Yossef R, Guttman O, Eini H, Azam T, Dinarello CA, Lewis EC. IL-1 Receptor antagonist chimeric protein: context-specific and inflammation restricted activation. J Immunol. 2015, 195:1705-12.

Segal E, Prestwood TR, van der Linden WA, Carmi Y, Bhattacharya N, Withana N, Verdoes M, Habtezion A, Engleman EG, Bogyo M. Detection of intestinal cancer by local, topical application of a quenched fluorescence probe for cysteine cathepsins. Chem Biol. 2015, 22:148-158.

Spitzer MH, Gherardini PF, Fragiadakis GK, Bhattacharya N, Yuan RT, Hotson AN, Finck R, Carmi Y, Zunder ER, Fantl WJ, Bendall SC, Engleman EG, Nolan GP. An interactive reference framework for modeling a dynamic immune system. Science. 2015, 349:1259425.

Carmi Y, Spitzer MH, Linde IL, Burt BM, Prestwood TR, Perlman N, Davidson MG, Kenkel JA, Segal E, Pusapati GV, et al. Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity. Nature. 2015, 521:99-104.

Carmi Y, Dotan S, Rider P, Kaplanov I, White MR, Baron R, Abutbul S, Huszar M, Dinarello CA, Apte RN, et al. The role of IL-1b in the early tumor cell induced angiogenic response. J Immunol. 2013, 190:3500-3509.

Carmi Y, Rinott G, Dotan S, Elkabets M, Rider P,
Voronov E, Apte, RN. Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis. J Immunol. 2013, 186:3462-3471.

Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov, E., White, M.R., Dinarello, C.A., and Apte, R.N. IL-1a and IL-1b recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol. 2011, 187:4835-4843.

Patents

• Engleman EG and Carmi Y. Methods and Compositions for Antibody and Antibody-Loaded Dendritic Cell Mediated Therapy. US2015012511
• Engleman EG, Spitzer M. and Carmi Y.  Methods and Compositions for Treating Individuals That Have Cander and for Identifying Individuals Responsive to Immunotherapy. 62/447,959

• 2017 Alon Award for Outstanding Young Scientists
• 2017 Swiss Bridge Award: Elucidating the Mechanisms by Which Tumor-Binding Antibodies Enable T Cells Infiltration into the Tumor Microenvironment