Infiltration of CD8 + T cells into tumor cell clusters in triple-negative breast cancer

Significance The infiltration of cytotoxic T cells into tumors is a critical factor in immunotherapy efficacy. We developed an algorithm to quantify infiltration level using whole-section immunohistofluorescence images from different patients. We observed consistent infiltration patterns of cytotoxic T cells (on the tumor cell cluster level) at the core and margin of each tumor. These spatial distributions enabled us to generate several hypotheses for mechanisms underlying the various infiltration levels. We used mathematical models to test which hypothetical mechanisms could recapitulate these patterns. One hypothesis, that of a fibrotic barrier, was shown to be unlikely. The other, involving a T cell chemorepellent, agrees with the data and can be tested in future experiments that directly measure the chemokine spatial patterns.