Cell Cycle Activity Correlates with Increased Anti-Tumor Immunity in Diverse Cancers
Abstract Objectives The cell cycle pathway regulating cell proliferation is overactivated in various cancers. Immune evasion is another important mechanism for tumor cell hyperproliferation. Nevertheless, the relationship between cell cycle and tumor immunity remains not fully understood. Materials and Methods Using the cancer genomics datasets for 10 cancer cohorts from the Cancer Genome Atlas (TCGA) program, we investigated the association between cell cycle activity (CCA) and anti-tumor immune signatures. We also explored the association between CCA and PD-L1 expression in these cancer cohorts. Moreover, we investigated the association between CCA and immunotherapy response in several cancer cohorts receiving immunotherapy. Results CCA likely exhibited positive associations with anti-tumor immune signatures (CD8+ T cell infiltration and immune cytolytic activity) in these cancer cohorts. The strong positive associations of CCA with DNA damage repair pathways and with tumor mutation load may explain the positive associations between CCA and anti-tumor immune signatures. Moreover, CCA displayed significant positive correlations with PD-L1 expression. Finally, we found that the enhanced CCA tended to be associated with unfavorable clinical outcomes in the TCGA cancer cohorts, though such association was not observed in the cancer cohorts receiving immune checkpoint blockade therapy. Conclusions CCA has significant positive associations with both anti-tumor immune signatures and tumor immune-suppressive signatures in diverse cancer types. Our findings provide new insights into cancer biology and potential clinical implications for cancer immunotherapy.