Explaining the Paucity of Intratumoral T Cells: A Construction Out of Known Entities.

Overview

This essay addresses the question of how tumors escape control by the immune system. The literature strongly points to inadequate accumulation of T cells among cancer cells as being the proximate cause, but this observation has no acceptable explanation as yet. An approach to this problem is adopted wherein the chemokines and chemokine receptors that normally mediate the trafficking of T cells to inflamed tissues are reviewed and considered in the context of their relative levels of expression in a transplanted colorectal tumor model. This method of reasoning-consistent with Bertrand Russell's (1985) advice, "Whenever possible, substitute constructions out of known entities for inferences to unknown entities"-leads to the proposal that signaling via the chemokine receptor, CXCR4, impairs the function of CXCR3 on the immune cells that are responsible for suppressing the growth of cancers.