Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high-grade serous ovarian cancer

Abstract

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 (CD8CT&IM) with the same margin localized CD45RO (CD45ROCT&IM) was the most robust prognostic predictor. Immune score (IS) was constructed by integrating FIGO stage with CD8CT&IM and CD45ROIM&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.