Spatial Cytotoxic And Memory T Cells In Tumor Predict Superior Survival Outcomes In Patients With High-Grade Serous Ovarian Cancer

Although the association between tumor-infiltrating CD3(+) T and CD8(+) T cells and superior survival in high-grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor-infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3(+) T, CD8(+) T, and CD45RO(+) cells in HGSOC. Different density of spatial localization of CD3(+) T, CD8(+) T, and CD45RO(+) cells exhibited heterogeneous association with OS. The combination of the center of the tumor and invasive margin localized CD8(+)T cells (CD8(CT&IM)) with the same margin localized CD45RO (CD45RO(CT&IM)) was the most robust prognostic predictor. Immune score (IS) was constructed by integrating FIGO stage with CD8(CT&IM) and CD45RO(IM&CT) and had the best prognostic value in HGSOC. The low-, intermediate-, and high-IS groups were observed in 44.7%, 41.6%, and 13.7% of patients, respectively. Low-IS identified patients were at higher risk of death compared to high-IS identified patients (HR = 12.426; 95% CI 5.317-29.039, p < 0.001); meanwhile, we evaluate the RMSTs over 10 years of follow-up and obtained RMST values of 104.09 months (95% CI 96.31-111.87 months) in the high-IS group, 75.26 months (95% CI 59.92-90.60 months) in the intermediate-IS group, and 48.68 months (95%CI 38.82-58.54 months) in the low-IS group. In general, spatial localization can modulate the clinical effects of TILs in HGSOC. Thus, the spatial expression of CD8 and CD45RO could aid clinicians to determine the follow-up plan of patients with HGSOC.