Our group aims to understand the roles dendritic cells (DCs) play in the development and response to treatment of cancer.
DCs are a key bridge between innate and adaptive immunity, and are essential for cancer immunotherapy. These cells can also serve as a direct immunotherapy target, with several dendritic cell targeting agents in clinical trials. Chief among these are CD40 agonistic antibodies, which have shown great promise as a cancer treatment by virtue of their ability to turn immunologically "cold" tumors "hot".
Immunologically “hot” or T cell inflamed tumors are associated with enhanced response to cancer immunotherapy through immune checkpoint blockade, and tumor T-cell inflammation is positively associated with tumor DC infiltration. Tumor features that promote or inhibit DC functions remain incompletely understood and we hypothesize that understanding these features can lead to new immunotherapy strategies to treat cancer.
We are developing mouse models to mechanistically dissect dendritic cell functions in cancer and inflammation as we believe that tumor-dendritic cell interactions are a critical determinant of tumor immunogenicity, and that dendritic cell functions are essential for durable cancer immunotherapy response.
Hackney JA, Misaghi S, Senger K, Garris C, Sun Y, Lorenzo MN, Zarrin AA DNA targets of AID evolutionary link between antibody somatic hypermutation and class switch recombination. Adv Immunol. 2009;101:163-89 - PMID: 19231595 - DOI: 10.1016/S0065-2776(08)01005-5
Garris CS, Wong JL, Ravetch JV, Knorr DA Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer. Sci Transl Med. 2021;13(594):ePub - PMID: 34011627 - PMCID: PMC8325152 - DOI: 10.1126/scitranslmed.abd1346
Algazi AP, Twitty CG, Tsai KK, Le M, Pierce R, Browning E, Hermiz R, Canton DA, Bannavong D, Oglesby A, Francisco M, Fong L, Pittet MJ, Arlauckas SP, Garris C, Levine LP, Bifulco C, Ballesteros-Merino C, Bhatia S, Gargosky S, Andtbacka RHI, Fox BA, Rosenblum MD, Daud AI Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma. Clin Cancer Res. 2020;26(12):2827-2837 - PMID: 32376655 - DOI: 10.1158/1078-0432.CCR-19-2217
Garris CS, Luke JJ Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response. Clin Cancer Res. 2020;26(15):3901-3907 - PMID: 32332013 - PMCID: PMC7607412 - DOI: 10.1158/1078-0432.CCR-19-1321
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