# Neoadjuvant chemotherapy-induced immune remodeling in ovarian cancer: implications for TIL dynamics and combination immunotherapy

## TL;DR

This review explores how neoadjuvant chemotherapy affects immune cells in ovarian cancer, focusing on TIL dynamics and potential for improved immunotherapy.

## Contribution

The paper systematically summarizes immune remodeling mechanisms post-NACT and proposes combination strategies for precision immunotherapy.

## Key findings

- NACT alters TIL density and composition, impacting chemotherapy response and prognosis.
- CD8+ T cells become spatially restricted in myelonets, leading to functional exhaustion.
- Dynamic TIL changes offer insights for developing biomarkers and combination therapies.

## Abstract

Ovarian cancer (OC), particularly high-grade serous ovarian cancer (HGSOC), is among the most lethal gynecologic malignancies, with its therapeutic challenges primarily stemming from a distinctly immunosuppressive tumor immune microenvironment (TIME). Neoadjuvant chemotherapy (NACT) has emerged as a crucial treatment strategy for advanced ovarian cancer; nevertheless, its impact on the tumor microenvironment—especially on tumor-infiltrating lymphocytes (TILs)—is not yet fully understood. As central mediators of antitumor immune responses, the density, composition, and dynamic changes of TILs are strongly associated with chemotherapy response and patient prognosis. Notably, spatial omics studies further revealed that, after NACT, a subset of CD8+ T cells can be confined within “myelonets” microdomains organized by myeloid cells, where interactions such as NECTIN2–TIGIT impose spatial restriction and induce functional exhaustion of T cells, thereby compromising their effective tumor killing. This review aims to systematically summarize the baseline characteristics and heterogeneity of lymphoid- and myeloid-derived TILs in ovarian cancer, elucidate the mechanisms underlying immune remodeling induced by NACT and their complex relationships with clinical outcomes, and further discuss combination therapeutic strategies and biomarker development based on dynamic TIL changes to enhance the clinical application of precision immunotherapy.