Abstract
BackgroundThe synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. Here, we investigated the systemic immune effects of CRT in patients with lung or head and neck cancer.Materials and methodsPeripheral blood mononuclear cells were collected at baseline and 1 month after treatment from blood samples of 29 patients treated with cisplatin-based chemoradiotherapy for lung or head and neck cancer. Circulating anti-tumor Th1 response was assessed by the ELISpot assay using a mixture of human leucocyte antigen (HLA) class II restricted peptides derived from telomerase (TERT). Phenotyping of circulating immunosuppressive cells (Treg and MDSC) was performed by flow cytometry.ResultsA significant increase of circulating Treg was observed in 60% of patients after CRT The mean rate of Treg was 3.1% versus 4.9% at baseline and after CRT respectively, p = 0.0015). However, there was a no significant increase of MDSC rate after CRT. In contrast, a decrease of tumor-specific Th1 response was documented in 7 out of 10 evaluated patients. We found high frequency of pre-existing tumor-specific Th1 response among patients with objective response after CRT compared to non-responders.ConclusionCisplatin-based CRT promotes expansion of Treg and decrease of circulating anti-tumor Th1 response in peripheral blood. The balance towards a sustained specific anti-tumor T-cell response appears to be associated with response to CRT.
Highlights
The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types
We found high frequency of pre-existing tumor-specific Th1 response among patients with objective response after CRT compared to non-responders
Tumor cells exposed to radiation therapy (RT) and/or CT release tumorassociated antigens (TAA) which are captured by dendritic cells (DCs) for processing and presentation on MHC class I and II molecules to T cells [5]
Summary
The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. We investigated the systemic immune effects of CRT in patients with lung or head and neck cancer. Tumor cells exposed to RT and/or CT release tumorassociated antigens (TAA) which are captured by dendritic cells (DCs) for processing and presentation on MHC class I and II molecules to T cells [5]. This leads to the priming and activation of effector T-cell responses against the TAA. The activated effector T cells traffic to tumor site where they recognize and kill their target cancer cells. RT can induce PD-L1 expression on both tumor cells and immune cells as well as upregulation of immune checkpoint receptors (TIGIT, TIM3 ...) on tumor infiltrative lymphocytes, limiting the anti-tumor immunity [13,14,15,16,17]
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