Characterization of the Immune Response to PD-1 Blockade during Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma.

Autor: Callejas-Valera JL; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA., Vermeer DW; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA., Lucido CT; Sanford School of Medicine, University of South Dakota, 1400 W 22nd Street, Sioux Falls, SD 57105, USA., Williamson C; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA., Killian M; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA., Vermeer PD; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA., Spanos WC; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA.; Sanford School of Medicine, University of South Dakota, 1400 W 22nd Street, Sioux Falls, SD 57105, USA., Powell SF; Sanford Research, 2301 East 60th Street North, Sioux Falls, SD 57104, USA.; Sanford School of Medicine, University of South Dakota, 1400 W 22nd Street, Sioux Falls, SD 57105, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 May 19; Vol. 14 (10). Date of Electronic Publication: 2022 May 19.
DOI: 10.3390/cancers14102499
Abstrakt: Background: Chemoradiotherapy is a standard treatment for HNSCC. Blockade of the PD-1/L1-2 interaction may represent a target to overcome immune escape during this treatment.
Methods: Utilizing a HNSCC mEERL C57BL/6 mouse model, we evaluated a PD-1 blockade alone or in combination with cisplatin-based chemoradiotherapy. Next, we evaluated peripheral blood mononuclear cells (PBMCs) with relative PD-1, TIM-3, and LAG-3 expression, and myeloid-derived suppressor-like (MDSC-like) populations from a clinical trial evaluating PD-1 blockade with chemoradiotherapy in HNSCC. Finally, we analyzed the effect of therapy on human T-cell clonality through T-cell Receptor (TCR) sequencing.
Results: Anti-PD-1 monotherapy induced no response in the mEERL model; however, combination with chemoradiotherapy improved tumor clearance and survival. PBMCs from patients treated with this combination therapy demonstrate a decline in circulating T-cell populations with knockdown of PD-1 expressing CD3+CD4+ and CD3+CD8+ T cells during treatment. However, TIM-3, LAG-3 expressing T-cell and MDSC-like populations concordantly rose. During treatment, the TCR repertoire demonstrates overall clonal expansion, with both unique and previously reported T-cell clones.
Conclusions: Our murine HNSCC model demonstrates efficacy of PD-1 blockade during chemoradiotherapy. However, while PD-1-expressing T cells decreased with this therapy, human PBMC findings also identified an increase in populations contributing to immune exhaustion. These findings further characterize PD-1 blockade during chemoradiotherapy for HNSCC and highlight potential competing mechanisms of immune evasion.
Databáze: MEDLINE
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