Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

SIMPLE SUMMARY: In this review, we present current knowledge about the prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) in ovarian cancer since this tumor shows a potential immunogenicity which makes it suitable for immunotherapy treatment; although, to date, the immunotherapy has not yielded the expected results. Understanding the factors which drive infiltration could be the key to unravel the clinical outcome heterogeneity in this cancer. Furthermore, understanding molecular mechanisms underlying the crosstalk between cancer and immune cells within the tumor microenvironment (TME) could help to identify and select subsets of OC patients who may benefit from immunotherapy. ABSTRACT: In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TILs. The abundant presence of TILs in OC suggests an immunogenic potential for this tumor. Despite the high immunogenic potential, OC has been described as a highly immunosuppressive tumor with a high expression of PD1 by TILs. Although further studies are needed to better define their role in prognostic stratification and the therapeutic implication, intraepithelial TILs represent a relevant prognostic factor to take into account in OC. In this review, we will discuss the promising role of TILs as markers which are able to reflect the anticancer immune response, describing their potential capability to predict prognosis and therapy response in OC.