Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis
Menée à l'aide de xénogreffes de cancer colorectal ou de cancer de la tête et du cou et menée à l'aide d'une technique d'imagerie, cette étude démontre que des cellules coliques cancéreuses peuvent, en interagissant avec les lymphocytes ayant infiltré la tumeur, acquérir par trogocytose des molécules régulatrices du système immunitaire
We have identified the presence of cancer cells harboring immune cell–specific surface marker proteins such as CD4 in the tumor microenvironment. Cancer cells acquired not only the T cell marker protein CD4 but also immune regulatory molecules such as CTLA4 by trogocytosis. Unlike other endocytic mechanisms, trogocytosis maintains the cellular localization and functions of the transferred membrane proteins. Therefore, trogocytic transfer of immune regulatory molecules enhances the immunosuppressive functions of cancer cells. This study provides insight into the interactions between cancer cells and tumor-infiltrating immune cells and how they contribute to the development of the immunosuppressive tumor microenvironment.Cancer cells can develop an immunosuppressive tumor microenvironment to control tumor-infiltrating lymphocytes. The underlying mechanisms still remain unclear. Here, we report that mouse and human colon cancer cells acquire lymphocyte membrane proteins including cellular markers such as CD4 and CD45. We observed cell populations harboring both a tumor-specific marker and CD4 in the tumor microenvironment. Sorted cells from these populations were capable of forming organoids, identifying them as cancer cells. Live imaging analysis revealed that lymphocyte membrane proteins were transferred to cancer cells via trogocytosis. As a result of the transfer in vivo, cancer cells also acquired immune regulatory surface proteins such as CTLA4 and Tim3, which suppress activation of immune cells [T. L. Walunas et al., Immunity 1, 405–413 (1994) and L. Monney et al., Nature 415, 536–541 (2002)]. RNA sequencing analysis of ex vivo–cocultured splenocytes with trogocytic cancer cells showed reductions in Th1 activation and natural killer cell signaling pathways compared with the nontrogocytic control. Cancer cell trogocytosis was confirmed in the patient-derived xenograft models of colorectal cancer and head and neck cancer. These findings suggest that cancer cells utilize membrane proteins expressed in lymphocytes, which in turn contribute to the development of the immunosuppressive tumor microenvironment.