Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer

Abstract

Epithelial ovarian cancer (EOC) is a significant cause of cancer-related mortality in women, and there has been no substantial decrease in the death rates due to EOC in the last three decades. Thus, basic knowledge regarding ovarian tumor cell biology is urgently needed to allow the development of innovative treatments for EOC. Traditionally, EOC has not been considered an immunogenic tumor, but there is evidence of an immune response to EOC in patients. Clinical data demonstrate that an antitumor immune response and immune evasion mechanisms are correlated with a better and lower survival, respectively, providing evidence for the immunoediting hypothesis in EOC. This review focuses on the immune response and immune suppression in EOC. The immunological roles of chemotherapy and surgery in EOC are also described. Finally, we detail pilot data supporting the efficiency of immunotherapy in the treatment of EOC and the emerging concept that immunomodulation aimed at counteracting the immunosuppressive microenvironment must be associated with immunotherapy strategies.

Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer

“…Epithelial tumor cell nests and stromal areas were measured using the Zeiss LSM Image Examiner. Myeloid subsets were manually counted in all representative images for either tumor epithelium, stroma, or both and were presented as the number of cells per mm 2 .…”

“…Conventional treatment (surgery combined with chemotherapy) results are poor; 75% of the patients with advanced disease develop recurrences, causing approximately 60-80% of patients to die within 5 y of initial diagnosis. [1][2][3] EOC consists of distinct histological subtypes. The most common subtype is serous carcinoma which accounts for about 70% of EOC.…”

Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer

“…7,8 In addition to a strong correlation between TIL infiltration and patient survival, there are also other important factors indicating ovarian cancer as a potential target for immunotherapy. Expression of multiple tumor-associated antigens provides targets for humoral and cellular immune responses.…”

Les récepteurs de nectines/nectines-likeDNAM-1 et CRTAM

“…Ces stratégies ne s'avèreront pleinement efficaces que si l'immunosuppression locale ou générale induite par la tumeur est inhibée conjointement [33,34]. Récemment, des résultats prometteurs ont été obtenus dans plusieurs essais cliniques ciblant des étapes clés de l'immunité adaptative à l'aide d'anticorps monoclonaux anti-CTLA-4 et/ou anti-PD-1 [35].…”