Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer
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Marina Baretti1, Qingfeng Zhu2, Wei Fu3, Jeffrey Meyer4, Hao Wang3, Robert A. Anders2 and Nilofer S. Azad1
1 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
2 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
3 Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
4 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Keywords: programmed death ligand 1; tumor-infiltrating lymphocytes; immune checkpoints; colorectal cancer; neoadjuvant chemoradiotherapy
Received: March 09, 2022 Accepted: June 28, 2022 Published: July 28, 2022
Introduction: DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. We investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients.
Materials and Methods: Tumor samples of rectal adenocarcinoma patients undergoing resection between 2008-2014 with (n = 62) or without (n = 17) nCRT treatment were collected. Sections were stained with CD8 and PD-L1 antibodies for immunohistochemistry. The prevalence of CD8+ cells was recorded in the tumor, interface tumor and background rectal side. Image analysis was used to determine the density of CD8+ lymphocytes. The percentage of PD-L1 expression was manually counted in tumor cells (TC), tumor stroma (TS) and the invasive front (IF). Mucin expression was determined as the percentage of the mucin area in the whole tumor area.
Results: PD-L1 expression on TCs was identified in 7.6% (6/79) of nCRT specimens (p = 0.33) and in none of the non-nCRT patients. Median densities of CD8+ infiltrating T lymphocytes did not differ significantly between the two groups. Mucin expression was significantly higher in the nCRT cohort (p = 0.02). Higher neutrophil to lymphocytes ratio (NLR) after nCRT was associated with worse outcome (HR = 1.04, 95% CI = 1.00–1.08).
Conclusions: nCRT exposure was associated with a non-significant difference in PD-L1 expression in rectal adenocarcinoma patients, possibly due to sample size limitations. Further mechanistic investigations and comprehensive immune analysis are needed to understand nCRT-induced immunologic shift in rectal cancer and to expand the applicability of checkpoint inhibitors in this setting.
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