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Macrophages selectively sense mechanical cell death in CLASP-depleted melanoma cells to trigger CXCL10 response
Otruba, Matúš ; Labzin, Larisa (advisor) ; Filipp, Dominik (referee)
Melanoma represents a significant and often fatal form of cancer, with metastasis being a primary cause of cancer-related deaths. Immunotherapy aims to stimulate the immune system to eliminate tumors, but even when used together with traditional chemotherapy, still only has <50% success rate. Chemotherapeutic drugs induce tumor cell death, primarily through apoptosis, which is 'silent' and does not incite inflammation or immune cell infiltration into the tumor. During metastasis, tumor cells migrate through confined spaces. CLASP proteins protect organelles and cellular integrity during tumor cell metastasis; when CLASP proteins are depleted, tumor cells migrating through tissue die through a mechanical cell death. The immunological impact of CLASP depletion-induced cell death remains unknown. This study aims to explore whether macrophages, innate immune cells that sense neighboring dying cells, trigger inflammatory cytokine responses specifically to mechanical, as opposed to chemotherapeutic, melanoma cell death. To model mechanical cell death during metastatic migration, CLASP1, a microtubule stabilizing protein, was depleted, and cells were physically compressed to simulate forces encountered during metastasis. Chemotherapy was simulated using a B-Raf inhibitor and the apoptosis inducer...
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