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

Abstract

Background: Immune checkpoint blockade has shown low response rates for advanced breast cancer, and combination strategies are needed. Microwave ablation (MWA) may be a trigger of antitumor immunity. This window-of-opportunity trial (ClinicalTrials.gov: NCT04805736) was conducted to determine the safety and feasibility of preoperative camrelizumab (an anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer.

Methods: 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.

Findings: 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⁺ T cells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8⁺ T cells showed higher cytotoxic activity and effector memory- and tumor-specific signatures than emergent clones after combination therapy. Enhanced interactions between clonal expansional CD8⁺ T cells and monocytes were observed, suggesting that monocytes contributed to the enhanced functions of clonal expansional CD8⁺ T cells. Major histocompatibility complex (MHC) class I-related pathways and interferon signaling pathways were activated in monocytes by combination therapy.

Conclusions: Camrelizumab combined with MWA was feasible for early-stage breast cancer. Peripheral CD8⁺ T cells were activated after combination therapy, dependent on monocytes with activated MHC class I pathways.

Funding: This study was supported by the Natural Science Foundation of Jiangsu Province (BK20230017).

Keywords: T lymphocytes; Translation to patients; breast cancer; immune checkpoint blockade; microwave ablation; monocytes.