The T cell-mediated tumor killing patterns revealed tumor heterogeneous and proposed treatment recommendation in ovary cancer.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, but the role of genes related to T cell-mediated tumor killing (TTK) sensitivity in ovarian cancer (OV) is unclear.

Methods: This study analyzed 1367 OV patients and 11 independent cohorts. The unsupervised clustering was conducted to identify three tumor subtypes based on genes that regulate tumor cell sensitivity to TTK (GSTTKs). The biological characteristics, genetic variations, immunological landscape, and therapeutic evaluation for each subtype were further explored.

Results: Patients were divided into three reproducible subtypes based on 61 GSTKKs associated with prognosis. C1 was likely to be an invasive subtype with the worst prognosis and highly unstable genome. C2 might be an immune-active subtype with the best prognosis, high immune infiltration and preferable response to immunotherapy. C3 might be a metabolic subtype, resistant to immunotherapy, but sensitive to drug therapy. Following an extensive exploration into a variety of distinct molecular features between the three subtypes, the results suggested that C2 patients were considered to derive significant efficacy from immunotherapy. For C1 and C3 patients, chemotherapy might be an ideal treatment strategy.

Conclusions: In this study, three GSTKKs-based subtypes were identified by assessing TTK patterns in OV. These new insights further improved our understanding of GSTTKs and might refine clinical treatment strategies for OV patients.