CD91 on antigen-presenting cells influences response to nascent tumors
The immune system is critical for detecting and eradicating aberrant, tumorigenic cells, and failure of the immunosurveillance system to target these nascent, emerging tumors leads to cancer development. In this episode, Robert Binder and colleagues determined that compared to WT animals, mice lacking the receptor CD91 on antigen-presenting cells are more susceptible to chemical-induced tumor formation as the result of underdeveloped early effector immune responses that in turn enable emergence of neo-antigen-expressing tumors. Moreover, in patients with lung squamous cell carcinomas and skin cutaneous melanomas, CD91 polymorphisms that affect ligand binding associated with poorer immune response. These results indicate that CD91 has potential to predict cancer risk and progression.
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Abstract
The immune system detects aberrant, premalignant cells and eliminates them before the development of cancer. Immune cells, including T cells, have been shown to be critical components in eradicating these aberrant cells, and when absent in the host, incidence of cancer increases. Here, we show that CD91, a receptor expressed on antigen-presenting cells, is required for priming immune responses to nascent, emerging tumors. In the absence of CD91, effector immune responses are subdued, and tumor incidence and progression are amplified. We also show that, consequently, tumors that arise in the absence of CD91 express neo-epitopes with indices that are indicative of greater immunogenicity. Polymorphisms in human CD91 that are expected to affect ligand binding are shown to influence antitumor immune responses in cancer patients. This study presents a molecular mechanism for priming immune responses to nascent, emerging tumors that becomes a predictor of cancer susceptibility and progression.
Authors
Abigail L. Sedlacek, Theodore P. Younker, Yu Jerry Zhou, Lisa Borghesi, Tatiana Shcheglova, Ion I. Mandoiu, Robert J. Binder
