Neoadjuvant chemotherapy modulates mast cell phenotypes and immune infiltration in high-grade serous carcinoma

The influence of neoadjuvant chemotherapy (NACT) on the immune landscape of high-grade serous carcinoma (HGSC) remains inadequately understood. This study aims to investigate the differential patterns of immune infiltration in HGSC tissues before and after NACT, as well as their clinical significance.

Immune infiltration patterns in HGSC tissues pre- and post-NACT were analyzed using our in-house RNA sequencing data (comprising 8 pre-NACT and 7 post-NACT tumor samples), three GEO datasets (GSE181597, GSE201600, GSE227666), and immunohistochemistry on 73 paired pre- and post-NACT samples. The response to NACT was evaluated using the Chemotherapy response score (CRS), categorizing patients as responders (CRS = 3) and non-responders (CRS = 1/2). Scissor and pseudotime analyses were conducted to investigate mast cell phenotype-associated cell populations and developmental trajectories utilizing single-cell RNA sequencing data (GSE165897).

NACT prompted dynamic alterations in immune cell infiltration, notably characterized by an increase in CD8+ T cells and mast cell infiltration, which were corroborated by immunohistochemistry. Following NACT, there was a notable increase in KIT expression, particularly among responders, whereas no significant difference was detected between responders and non-responders prior to NACT. Elevated KIT expression was linked to a poor prognosis. There was a transition from CD52 + KIT+ mast cells to JUN+/TNFRSF12A+ subsets post-NACT.

Successful NACT was associated with a reduction in CD52 + KIT+ mast cells and an increase in the JUN+/TNFRSF12A+ subpopulation. The increased infiltration of KIT-expressing mast cells may serve as a prognostic biomarker for HGSC following NACT and represent a potential novel therapeutic target to enhance NACT efficacy.