Bowel Cancer and Biomarker Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.
Department of Radiation Oncology, Royal North Shore Hospital, Sydney, Australia.
Oncoimmunology. 2023 Jul 20;12(1):2238506. doi: 10.1080/2162402X.2023.2238506. eCollection 2023.
Approximately 20% of locally advanced rectal cancer (LARC) patients treated preoperatively with chemoradiotherapy (CRT) achieve pathologically confirmed complete regression. However, there are no clinically implemented biomarkers measurable in biopsies that are predictive of tumor regression. Here, we conducted multiplexed immunophenotyping of rectal cancer diagnostic biopsies from 16 LARC patients treated preoperatively with CRT. We identified that patients with greater tumor regression had higher tumor infiltration of pan-T cells and IRF8HLA-DR cells prior to CRT. High IRF8HLA-DR cell density was further associated with prolonged disease-specific survival with 83% survival at 5 y compared to 28% in patients with low infiltration. Contrastingly, low CD11c myeloid cell infiltration prior to CRT was a putative biomarker associated with longer 3- and 5-y disease-free survival. The results demonstrate the potential use of rectal cancer diagnostic biopsies to measure IRF8 HLA-DR cells as predictors of CRT-induced tumor regression and CD11c myeloid cells as predictors of LARC patient survival.
约 20%接受术前放化疗 (CRT) 的局部晚期直肠癌 (LARC) 患者可达到病理证实的完全消退。然而，目前在活检中尚无可测量的、预测肿瘤消退的临床实施的生物标志物。在这里，我们对 16 名接受术前 CRT 的 LARC 患者的直肠肿瘤诊断活检进行了多重免疫表型分析。我们发现，在 CRT 前，肿瘤消退程度较高的患者存在更多的泛 T 细胞和 IRF8HLA-DR 细胞浸润。高 IRF8HLA-DR 细胞密度与疾病特异性生存率延长相关，5 年生存率为 83%，而浸润程度低的患者为 28%。相反，CRT 前低 CD11c 髓样细胞浸润是与 3 年和 5 年无病生存率延长相关的潜在生物标志物。这些结果表明，直肠肿瘤诊断活检可用于测量 IRF8 HLA-DR 细胞作为 CRT 诱导的肿瘤消退的预测因子，以及 CD11c 髓样细胞作为 LARC 患者生存的预测因子。
