Association between peripheral CX3CR1⁺ CD8⁺ T cell dynamics and pathological response to pembrolizumab-containing neoadjuvant chemotherapy in triple-negative breast cancer

Reliable blood-based biomarkers that predict response to immune checkpoint inhibitor (ICI)–containing neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC) remain limited. CX3C chemokine receptor 1 (CX3CR1) expression on CD8⁺ T cells has emerged as a dynamic biomarker of response to ICI therapy in non–small cell lung cancer; however, its utility in TNBC remains unclear. We investigated whether dynamic changes in peripheral blood (PB) CX3CR1⁺ CD8⁺ T cells are associated with response to pembrolizumab-containing NAC in patients with TNBC. Serial PB samples were collected from 12 patients with early-stage TNBC undergoing pembrolizumab-containing NAC. The frequency of CX3CR1⁺ cells among CD8⁺ T cells was analyzed by flow cytometry before and during treatment. Associations between CX3CR1⁺ CD8⁺ T cell dynamics and tumor shrinkage, pathological complete response (pCR), and immune-related adverse events (irAEs) were evaluated. Baseline frequencies of CX3CR1⁺ CD8⁺ T cells were not associated with pCR. However, dynamic changes in CX3CR1⁺ CD8⁺ T cells were moderately correlated with tumor shrinkage ( r = 0.58, p = 0.04), whereas changes in absolute lymphocyte count showed no such association ( r = − 0.07, p = 0.82). All patients who achieved pCR exhibited ≥ 20% increase in CX3CR1⁺ CD8⁺ T cells during treatment at least once, compared with only one of seven patients who did not achieve pCR. No statistically significant association between treatment-induced changes in the frequency of CX3CR1⁺ CD8⁺ T cells and the occurrence of grade 3 irAEs was observed in this small cohort ( p = 0.99). Dynamic increases in PB CX3CR1⁺ CD8⁺ T cells during pembrolizumab-containing NAC were associated with treatment response in patients with TNBC, suggesting that CX3CR1 dynamics may serve as a blood-based marker of on-treatment response.