Pawel Kalinski, MD, PhD
Photo: Pawel Kalinski

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716.845.7629

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Elected 2015
My research evaluates the interactions of the immune cells with lymph node and tumor microenvironments, aiming to incorporate immunotherapy into comprehensive cancer care. We have established that dendritic cells (DCs) “memorize” the inflammatory signals received during their development and translate them into distinct patterns of immunity induced in the draining lymph nodes. These findings have led to the concept of “signal 3” as the third signal (additional to antigenic- and costimulatory signals) delivered by DCs to T lymphocytes and regulating T cell effector functions (Th1, Th2, Th17, effector-memory, central memory). The associated concepts of functional polarization of DCs and polarized DCs subsets have resulted in clinical applications of type-1 polarized DCs (generated in the inflammatory conditions mimicking viral infections) in order to selectively promote type-1 immunity against cancer. Our follow up studies have demonstrated that differentially-polarized DCs secrete different sets of chemokines and that DC polarization can be used to selectively direct vaccine antigens to naïve, effector and memory T cells, rather than to undesirable Treg cells. Extending these studies, we have developed combinatorial adjuvants to augment the entry of immune cells into lymph nodes and to reprogram tumor micro-environments for selectively enhanced entry of CTLs and Th1 cells (spontaneously-arising, vaccination-induced or adoptively-transferred) while counteracting local accumulation of Tregs and MDSCs. The resulting treatments are being currently tested in clinical trials in melanoma, CTCL, colorectal-, prostate- , ovarian-, and brain cancers. Our follow up studies have demonstrated that differentially-polarized DCs secrete different sets of chemokines and that DC polarization can be used to selectively direct vaccine antigens to naïve, effector and memory T cells, rather than to undesirable Treg cells. Extending these studies, we have developed combinatorial adjuvants to augment the entry of immune cells into lymph nodes and to reprogram tumor micro-environments for selectively enhanced entry of CTLs and Th1 cells (spontaneously-arising, vaccination-induced or adoptively-transferred) while counteracting local accumulation of Tregs and MDSCs. The resulting treatments are being currently tested in clinical trials in melanoma, CTCL, colorectal-, prostate- , ovarian-, and brain cancers.