Fig. 4

Bioinformatic evidence of the effects of necroptosis, ferroptosis, and pyroptosis on T cell dysfunction and CD8+ T cell infiltration based on molecular signatures. a The effects of necroptosis, ferroptosis, and pyroptosis on T cell dysfunction and CD8+ T cell infiltration were evaluated based on the molecular signatures of four sets with 37 independent cohorts (core cohorts, immunotherapy datasets, CRISPR screen datasets, and datasets of immunosuppressive cell types). The core cohorts consisted of the five most confident results obtained using gene expression data, and a high z-score (red) suggests that the indicated gene promotes T cell dysfunction. The immunotherapy datasets consisted of 12 datasets of patients who received either ICIs or ACT. In this set, a high z-score (red) represents an unfavorable role of the indicated gene in improving the effects of immunotherapy. CRISPR screening of mouse cancer cells identified genes whose knockout enhanced the efficacy of T cell-mediated tumor cell killing based on 17 cohorts; in these studies, a z-score < 0 (blue) reflects the downregulation of the indicated gene after an increase in either T cell function or the efficacy of immunotherapy, suggesting the negative effects of the indicated gene on immunotherapy outcomes. Immunosuppressive cells restrict the tumor infiltration of T cells, including cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), and the M2 subtype of tumor-associated macrophages (TAMs). This section presents the gene expression levels in these T cell exclusion signatures, and a high z-score (red) indicates that the specified gene is overexpressed in immunosuppressive cells. b An example of the evaluation of T cell dysfunction. A considerable amount of CTL infiltration predicts prolonged survival only in tumor samples from patients with low SLC7A11 expression, suggesting that SLC7A11 potentially promotes T cell dysfunction. c The effects of necroptosis, ferroptosis, and pyroptosis on CD8+ T cell infiltration based on molecular signatures are shown