Ferroptosis and Cancer Immunotherapy

Abstract

Traditional treatment strategies of cancer are far from satisfaction. As a non-apoptotic cell death process and owning to the characteristics of iron-dependent lipid peroxide accumulation, ferroptosis has become a new target of tumor treatment. Numerous studies have proved that ferroptosis could enhance the immunogenicity of cancer and interact with immune cells. Cancer antigens, exposed to cancer cells underwent ferroptosis, effectively improve the immunogenicity of the tumor microenvironment and promote the activation and maturation of immune cells. Meantime, immune cells release immunostimulatory cytokines including TNF-α and IFN-γ to downregulate the expression of SLC7A11 and SLC3A2, and reduce the absorption of cysteine, leading to lipid peroxidation and iron deposition in cancer cells. Consequently, induction of ferroptosis via iron deposition-based combination strategies could stimulate and activate natural and adaptive immune response which release immune-stimulating factors to induce iron deposition in cancer cells. In this review, we provided a critical analysis of the correlation between ferroptosis and immune, providing a novel way that how to effectively induce ferroptosis in cancer which maybe one of the focuses in future to improve the development of new therapeutic strategies of cancer.

Integrated analysis of FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer and anti-proliferation of T lymphocyte

“…SLC3A2 is a key chaperone for xCT in the process of ferroptosis, metabolism and proliferation in cancer cells [31][32][33]. Owing to these diverse molecular functions, overexpression of SLC3A2 has been found associated with the development and progression of various types of cancer.…”

Neddylation pattern indicates tumor microenvironment characterization and predicts prognosis in lung adenocarcinoma

“…Many studies have shown that multiple factors are involved and controlled in tumorigenesis. Sustained growth signaling, unlimited replication potential, antiapoptotic factors, acquisition of invasive metastasis, reprogramming of cell metabolism, and TME are major hallmarks of cancer malignancy ( Hanahan and Weinberg, 2011 ; Wong, 2011 ; Mossmann et al, 2018 ; Xiao and Yu, 2021 ; Yin et al, 2022 ). However, tumors exhibit extreme heterogeneity, which is characterized by mutations in genes and alterations in the TME ( Paul et al, 2019 ; Zhang et al, 2022 ).…”

Ferroptosis, Metabolic Rewiring, and Endometrial Cancer

“…Thus, ferroptosis is an immunogenic cell death. This additional tumor suppression mechanism could be successfully exploited in immunotherapy [ 20 ]. For example, nanoparticles charged with RSL-3 not only initiated T lymphocyte activation and antitumoral response but also increased resistance to lipid damage repair in tumor cells, leading to accumulation of ROS [ 73 ] and sensitivity to radiotherapy [ 74 ].…”

“…Thus, ferroptosis can be used to eliminate tumor cell subpopulations responsible for cancer recurrence. To increase the anticancer effect, ferroptosis can be coupled with chemotherapy [ 17 ], radiation therapy [ 18 ], photodynamic therapy [ 19 ], and, being an immunogenic cell death, with immunotherapy [ 20 ].…”