Background: NSCLC induces pro-tumorigenic immunosuppressive changes to evade the immune system. Response of tumors to therapy, including to immunotherapy, depends on interactions of epithelial tumor cells and the microenvironment. Ex vivo culture (EVOC) models directly established from fresh NSCLC tumor tissues can be used as a complete model that resembles real tumor and its microenvironment. Little is known about the impact of drugs such as chemotherapy, radiotherapy or targeted agents on the expression and activity of the PD1-PDL1 signaling in human cancers. Combining such treatments with immunotherapy seems to be a promising approach that is actively investigated. We are using an EVOC model to study the impact of anti-PDL1 agents in NSCLC, alone or in combination with other therapeutics (chemotherapy or radiotherapy). Results: Our results indicate our EVOC model applicability as modeling immunotherapy effects in cancer. Specifically, tumor and stromal cells are maintained with a stable structure over a time window of several days and cell death is seen in response to cytotoxic drugs. Importantly, PDL1 is dramatically induced in response to inflammation signals (e.g. IFNg), PDL1 is reduced in response to steroids and variability in PDL-1 expression is seen between EVOCs from different NSCLC patients. Conclusions: NSCLC EVOC is a promising model for elucidation of immunotherapy and other drugs impact on real human cancer with its native microenvironment and immune cells.
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