Ovarian Carcer Immunology and Immunotherapy: Editorial Note

As the guest editor of the Special Issue on Ovarian Cancer Immunology Immunotherapy, I would like to include certain brief comments on the current state of the field and to introduce the Special Issue. Ovarian carcinoma and malignant melanoma are the first human tumors where immune responses, primarily restricted to autologous tumor cells, were first demonstrated. T-cell lines and clones developed in recombinant interleukin-2 (rIL-2) from tumor-infiltrating lymphocytes (TIL) from these tumors exhibited cytotoxicity and/or cytokine production, primarily restricted to autologous tumor cells. The T-cell receptor (TCR) and the CD3 differentiation antigen on effector T cells and HLA on target tumor cells, are critical molecules of the T-cell anti-tumor responses. Subsequent studies demonstrated that peptides, derived from tumor antigens and presented to T cells by self-HLA are recognized. These anti-tumor T cell responses are trimolecular complex (TCR/peptide/HLA) immune responses.

The tumor microenvironment (TMI) in ovarian cancer is crucial in determining the ability of the immune responses of the host to control tumor growth. Complex interactions in the TMI between the effector T cells, the tumor cells and immunosuppressive cells (Tregs, myeloid-derived suppressor cells, and monocytes/macrophages) and molecules (tumor-growth factor-beta and IL-10) are critical for the outcome of the immune responses against the tumor.

The demonstration of anti-tumor responses in ovarian cancer resulted in the development of several immunotherapy approaches for the treatment of these patients, including: (i) Adoptive T-cell therapy using rIL-2-expanded TIL; (ii) immune checkpoint inhibitors; (iii) CAR T-cell immunotherapy; and (iv) combinations of the above approaches alone, as well as combinations of them with chemotherapy. Certain of these approaches have shown promise for treating patients with ovarian cancer refractory to platinum-based chemotherapy; others are at an earlier stage of evaluation/development. Additional approaches, such as CRISPR gene editing, should be included. These treatment approaches should be used to develop combined new treatment modalities for these patients. The development of new and more effective combination approaches is urgently needed. Even in the best reported series five years survival of patients with ovarian cancer is approximately 50% and the patients will eventually succumb to the disease or its complications.

The contributions to the Special Issue reflect interactions of effector antitumor T cells, tumor cells, and immunosuppressive cells and molecules in the TMI, as well as issues addressing the development of combination therapies. Among others, polymorphisms of inflammatory cytokine genes were evaluated, and risk as well as protective genotypes were identified. The authors suggest that genetically modulated inflammation is driving epithelial ovarian carcinoma. The prognostic significance of the AP-1 transcription factor and its association with FOS and JUN molecules was investigated in another report. It was concluded that JUNB-containing AP-1 dimers are associated with “immune cold” infiltrating immune cells and may promote tumor progression. Other studies involve the evaluation of ascites as potential biological surrogates for molecular characterization of tumor tissue in ovarian cancer. The association of serum IgG antibodies to C. trachomatis with increased risk to borderline ovarian tumors, but not epithelial ovarian carcinoma, is reported in another study. Metabolic pathways affecting immune escape mechanisms of different types of ovarian cancer are also addressed in this issue. Metastasis of other tumors to the ovaries is investigated in other reports as well as the recurrence and malignant transformation of borderline ovarian tumors.

• Copyright © 2026 The Author(s). Published by the International Institute of Anticancer Research.