FIGURE 2.

Immune profile of anti-PD-1/PD-L1 antibody-treated tumor patients associated with improved clinical outcome or therapy resistance. A high T effector gene signature expression in pretherapy tumor samples is associated with improved survival of anti-PD-L1- and anti-VEGF-treated cancer patients. In addition, responders to anti-PD-1 treatment show a higher frequency of intratumoral CD8⁺ T cells at baseline and an increased frequency of tumor-infiltrating CD8⁺ T cells during therapy. Furthermore, they also have a higher proportion of intratumoral memory-like CD8⁺ T cells. The presence of PD-1^T CD8⁺ T cells, which are characterized by a high PD-1 expression and by the capability to secrete CXCL13, is also correlated with improved clinical outcome of anti-PD-1-treated cancer patients. Moreover, an increased frequency of TCF7⁺PD-1⁺CD8⁺ T cells in pretreatment tumor samples is associated with prolonged survival in patients treated with anti-CTLA-4 and anti-PD-1-antibodies. An increased density of B cells and TLS, consisting of a DC-containing T cell zone and a follicular DC-containing B cell zone, in pretreatment tumor samples is also correlated with an increased survival of anti-PD-1-treated patients. Furthermore, a higher PD-L1 expression on tumor cells and tumor-infiltrating immune cells is correlated with better clinical responses to anti-PD-1/PD-L1 therapy. In contrast, high frequencies of exhausted CD8⁺ T cells and PD-1⁺CD38^hiCD8⁺ T cells in tumor tissues are associated with resistance to anti-PD-1 therapy. Non-responders to anti-PD-L1 and anti-VEGF therapy also show a high myeloid inflammation gene expression signature.