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The Cellular Basis for the Cancer-Related Phenomena of Immune Suppression and Cachexia

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Although cancers elicit immune responses, they occur. This paradox must be understood to improve cancer immunotherapy. “Stromal” cells (all non-cancer cells in the tumor) prevent cancer-specific immune responses from controlling tumor growth, but the diversity of this population has hindered identification of the relevant cell type. We developed a mouse model that enables the conditional ablation of a stromal cell type that was recognized 20 years ago by its expression of the membrane protein, “fibroblast activation protein-alpha”, or FAP . Ablating FAP stromal cells causes immune-mediated necrosis of established tumors. FAP cells reside also in skeletal muscle where their depletion leads to a wasting condition resembling cancer cachexia. Thus, the redistribution of the FAP + cell from normal tissues to tumors may link the cancer-related phenomena of immune suppression and cachexia.

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