Preoperative single-dose camrelizumab and/or microwave ablation in women with early-stage breast cancer: A window-of-opportunity trial

Abstract

Immune checkpoint blockade has shown low responserates for advanced breast cancer, and combination strategiesareneeded. Microwave ablation (MWA) may be a triggerofantitumor immunity. This window-of-opportunity trial (ClinicalTrials.gov: NCT04805736) was conducted to determine the safetyand feasibility of preoperative camrelizumab (an anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer. Sixty participants were randomized to preoperatively receive single-dose camrelizumab alone (n= 20), MWA alone (n= 20), or camrelizumab+MWA (n= 20). A random number table was used to allocate interventions. The primary outcome was the safety and feasibility of MWA combined with camrelizumab. Camrelizumab and MWA were well tolerated alone and in combination without delays in prescheduled surgery. No treatment-related grade III/IV adverse events were observed. Different from in the single-dose camrelizumab or MWA group, participants showed stable counts of blood cells after combination therapy. After combination therapy, peripheral CD8+ Tcells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8+ Tcells showed higher cytotoxic activity and effector memory- and tumor-specific signatures than emergent clones after combination therapy. Enhanced interactions between clonal expansional CD8+ Tcells and monocytes were observed, suggesting that monocytes contributed to the enhanced functions of clonal expansional CD8+ Tcells. Major histocompatibility complex (MHC) class I-related pathways and interferon signaling pathways were activated in monocytes by combination therapy. Camrelizumab combined with MWA was feasible for early-stage breast cancer. Peripheral CD8+ Tcells were activated after combination therapy, dependent on monocytes with activated MHC class I pathways. This study was supported by the Natural Science Foundation of Jiangsu Province (BK20230017).