Pyroptosis, ferroptosis, and autophagy in immune therapy: perspective for immunotherapy of endometrial cancer

Aim

Endometrial cancer (EC) is one of only a few malignant conditions for which both incidence and mortality are currently rising. Immunotherapy has become an effective treatment modality for patients with advanced disease following standard therapy. However, immune checkpoint inhibitors (ICIs) are significantly limited. The existence and physiological significance of programmed cell death (PCD) pathways distinct from apoptosis have garnered increasing interest in recent years. This review aims to summarize the evidence of the association between antitumor immunity and non-apoptotic RCD.

Methods

Papers published up to March 31, 2024, in the PubMed, Web of Science, and Google Scholar databases were included in this review.

Results

Therapeutic options for EC treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Immune checkpoint blockade (ICB) therapy, with PD-1/PD-L1 blockade therapy as the most typical representative, has significantly changed the current cancer treatment landscape. A growing body of evidence suggests the potential application of targeting non-apoptotic RCD to enhance the efficacy of immunotherapy in malignancy.

Conclusions

This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, and pyroptosis, and the potential application of non-apoptotic RCD to improve the efficacy of immunotherapy in endometrial cancer and discusses future perspectives.

Purpose of Review

Immunotherapy represented by ICIs has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs. In this review, we reveal broad crosstalk between anticancer immunity and nonapoptotic cell death mechanisms based on existing laboratory and bioinformatic evidence.

Recent Findings

Involvement of non-apoptotic RCD in tumor biological regulation. It plays an important role in the occurrence, development, and metastasis of tumors. RCD has been widely studied in malignant tumors, and more and more evidence shows that pyroptosis, ferroptosis, and autophagy are closely related to the occurrence and progression of EC.