Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Oncotarget. 2022 Jul 28;13:907-917. doi: 10.18632/oncotarget.28255. eCollection 2022.
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.
Tumor samples of rectal adenocarcinoma patients undergoing resection between 2008-2014 with ( = 62) or without ( = 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.
PD-L1 expression on TCs was identified in 7.6% (6/79) of nCRT specimens ( = 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 ( = 0.02). Higher neutrophil to lymphocytes ratio (NLR) after nCRT was associated with worse outcome (HR = 1.04, 95% CI = 1.00-1.08).
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.
DNA 损伤和由此产生的新抗原形成被认为是放射治疗和 PD-1/PD-L1 通路抑制协同作用的机制，可诱导抗肿瘤免疫反应。我们研究了新辅助放化疗（nCRT）诱导的直肠腺癌患者肿瘤浸润性 CD8+T 淋巴细胞、PD-L1 和粘蛋白表达的变化。
收集了 2008-2014 年间接受直肠腺癌切除术的患者（nCRT 治疗组 n=62，无 nCRT 治疗组 n=17）的肿瘤样本。用 CD8 和 PD-L1 抗体进行免疫组织化学染色。记录肿瘤、肿瘤界面和背景直肠侧 CD8+细胞的发生率。采用图像分析确定 CD8+淋巴细胞的密度。手动计数肿瘤细胞（TC）、肿瘤基质（TS）和侵袭前沿（IF）中 PD-L1 的表达百分比。粘蛋白表达确定为整个肿瘤面积中粘蛋白面积的百分比。
nCRT 标本中 7.6%（6/79）（ = 0.33）存在 TC 上的 PD-L1 表达，而无 nCRT 患者均不存在。两组间 CD8+浸润 T 淋巴细胞的密度无显著差异。nCRT 组的粘蛋白表达明显更高（ = 0.02）。nCRT 后中性粒细胞与淋巴细胞比值（NLR）较高与预后较差相关（HR=1.04，95%CI=1.00-1.08）。
nCRT 暴露与直肠腺癌患者 PD-L1 表达无显著差异相关，可能是由于样本量有限。需要进一步进行机制研究和全面的免疫分析，以了解 nCRT 诱导的直肠癌免疫变化，并扩大检查点抑制剂在该环境中的适用性。
