A combination of radiotherapy and chemotherapy (CRT: chemoradiation) is particularly used as a cytotoxic therapy in locally advanced cancers. CRT also gained great interest as a combination approach with immune checkpoint inhibitors (ICI). In this regard, our recent report showed in the murine tumor microenvironment that CRT synergistically improves the antitumor T cell immunity suitable for ICI action (Lauret et al, JITC, 2021). Here, we performed a high throughput blood-based immune analysis in head and neck squamous cell carcinoma (HNSCC) treated by CRT.
Forty-eight HNSCC patients were enrolled in the i-CRT cohort (NCT03117946). Blood samples were collected before (BSL), on day 15, and 3 months after platinum-based CRT. Tumor-specific T cell responses were measured by IFN-γ ELISpot using a mixture of peptides derived from telomerase and NY-ESO-1. Flow cytometry was used for phenotypic and functional characterization (exhaustion, polarization, function) of circulating T cells and for immune suppressive cell monitoring. Bulk RNA sequencing was performed to analyze transcriptomic signatures from blood immune cells at different times.
Twenty-five out of 40 (62%) evaluable patients had pre-treatment circulating anti-tumor T cell responses. A transient decrease in this response occurred two weeks after CRT and most patients (85%) recovered their immune responses 3 months after CRT. These circulating T cells induced after CRT displayed a Th1-polarized profile with upregulation of IFN-γ, TNF-α, and IL-2 expression. Furthermore, early blood expansion of exhausted phenotype T cells co-expressing PD-1+ TIM-3+ TIGIT+ was detected after CRT together with MDSC expansion. Patients with high adaptive antitumor T cell response at baseline showed improved clinical outcomes. Transcriptomic analysis from PBMC support that CRT responders displayed upregulation of inflammatory-, M1 macrophages-, Th1 polarization-, and T cell memory-associated gene signatures while Treg, M2, neutrophils, and T cell exhaustion were downregulated.
These results provide insight into the systemic immunological changes that occurred during CRT which should be taken into account for combining CRT with immunotherapy.
NCT03117946.
UMR1098.
Ligue Contre le Cancer, the Bourgogne Franche Comte Regional Council, the ARC and the Canceropole EST.
All authors have declared no conflicts of interest.