C. Marcela Diaz Laboratory

Research

Overview

The main research focus of our laboratory pertains to elucidating the mechanisms that mediate the optimal induction of anti-tumor immune responses. To accomplish this, we have developed a preclinical model that recapitulates the generation of protective anti-tumor immune responses in the setting of adoptive cell transfer. Using this model, we have previously demonstrated unique biological traits of ex vivo activated T cells that have important implications for the design of clinical trials that utilize adoptive cell therapy. We have also developed tumor models with variable levels and types of inflammation with the goal of understanding how intratumoral inflammation influences the factors that promote or inhibit anti-tumor immune responses. We collaborate with solid tumor oncologists in several projects aimed at elucidating the mechanisms behind resistance to immunotherapy. Our group was one of the first to demonstrate the clinical relevance of myeloid derived suppressor cells in cancer and we currently focus on understanding the factors that promote MDSC function.

Our ongoing projects include:

• Identifying the traits of activated anti-tumor T cells that associate with enhanced survival, homing and cytotoxic function. Our model of productive adoptive T cell therapy involves the ex vivo expansion of T cells in the presence of IL-12.  We have modified the conditions of T c ell expansion and/or transfer to mimic both productive and non-productive T cell-mediated anti-tumor responses. We are using this model to elucidate the immune determinants that are required for clinically beneficial T cell mediated responses induced after adoptive transfer.
  
  
• Characterizing the inflammatory mediators that promote and/or impede effective anti-tumor responses.  We are utilizing tumor cell lines that mediate varying levels of inflammation to identify the stromal cell sources responsible for the production of the functionally relevant products that govern a pro-tumor or anti-tumor inflammatory state.  These findings will provide the scientific rationale for devising synergistic combinatorial strategies that target the relevant mediators with the goal of enhancing the effectiveness of checkpoint blockade.

• We are using preclinical models and patient-derived materials for in vivo and in vitro functional assays as well as immunogenomic profiling to understand the mechanisms that mediate the elicitation and function of MDSCs and their impact on responses to immunotherapy. 

Selected Publications

View publications for C. Marcela Diaz, PhD
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Díaz-Montero CM, Salem ML, Garrett-Mayer E, Cole DJ, Montero AJ. Increased Levels of Circulating Myeloid-Derived Suppressor Cells In Whole Blood Correlate With Advanced Clinical Cancer Stage, Increased Tumor Burden, and Cyclophosphamide Containing Chemotherapy in Solid Tumor Patients. Cancer Immunol Immunother. 2009 Jan;58(1):49-59.

Najjar YG, Rayman PA, Jia X, Pavicic PG, Rini BI, Tannenbaum CS, Ko J, Haywood S, Cohen PA, Hamilton T, Díaz Montero CM, Finke JH. Myeloid derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL-1β, IL-8, CXCL5 and Mip-1α. Clin Cancer Res. 2017 May 1;23(9):2346-2355.

Lin L, Rayman P, Pavicic PG Jr, Tannenbaum C, Hamilton T, Montero A, Ko J, Gastman B, Finke J, Ernstoff M, Díaz-Montero CM.  Ex vivo conditioning with IL-12 protects tumor-infiltrating CD8+ T cells from negative regulation by local IFN-γ.  Cancer Immunol Immunother. 2019 Mar;68(3):395-405

Tannenbaum CS, Rayman PA, Pavicic PG, Kim JS, Wei W, Polefko A, Wallace W, Rini BI, Morris-Stiff G, Allende DS, Hamilton T, Finke JH, Díaz-Montero CM. Mediators of Inflammation-Driven Expansion, Trafficking, and Function of Tumor-Infiltrating MDSCs. Cancer Immunol Res. 2019 Aug 22.

Díaz-Montero CM, Rini BI, Finke JH.  The Immunology of Renal Carcinoma.  Nature Reviews Nephrology.  2020 Dec;16(12):721-735.