Kitagawa Yusuke, Akiyoshi Takashi, Yamamoto Noriko, Mukai Toshiki, Hiyoshi Yukiharu, Yamaguchi Tomohiro, Nagasaki Toshiya, Fukunaga Yosuke, Hirota Toru, Noda Tetsuo, Kawachi Hiroshi
Gastroenterological Center, Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, TYO, Japan.
Gastroenterological Center, Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, TYO, Japan.
Clin Colorectal Cancer. 2022 Mar;21(1):e1-e11. doi: 10.1016/j.clcc.2022.01.004. Epub 2022 Jan 11.
Elevated tumor-infiltrating T-cell density is associated with favorable outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Here, we evaluated the significance of programmed cell death 1 (PD-1)-positive cells, regulatory T cells, and macrophages in response to CRT and prognosis.
We assessed CD8+, PD-1+, FOXP3+, CD68+, and CD163+ intratumoral and stromal cell densities by immunohistochemistry using pre-treatment biopsies from 275 patients with rectal cancer treated with neoadjuvant CRT. We determined the impact of these measurements on response to CRT and survival. Response to CRT was determined by tumor regression grade (TRG) of surgical specimens, with good responders defined as TRG3-4.
Intratumoral CD8+ and PD-1+ cell densities were significantly higher in good responders than in poor responders, whereas stromal CD68+ cell density was significantly lower in good responders as compared with poor responders. The multivariable analysis revealed high intratumoral CD8+ and PD-1+ cell densities to be independently associated with good responders (CD8: odds ratio [OR], 2.27; 95% confidence interval [CI], 1.21 - 4.34, P = .010; PD-1: OR, 1.97; 95%CI, 1.03 - 3.84, P = .039), and improved recurrence-free survival (CD8: hazard ratio [HR], 0.56; 95%CI, 0.32 - 0.98, P = .044; PD-1: HR, 0.37; 95%CI, 0.19 - 0.71, P = .002). Only high intratumoral CD8+ cell density was associated with improved overall survival (P = .022).
Pre-treatment high intratumoral PD-1+ and CD8+ cell densities were independently associated with good response to CRT and improved recurrence-free survival, with high intratumoral CD8+ cell density additionally associated with improved overall survival. These values may serve as predictive and prognostic biomarkers in rectal cancer.
在接受新辅助放化疗（CRT）的直肠癌患者中，肿瘤浸润性T细胞密度升高与良好预后相关。在此，我们评估了程序性细胞死亡1（PD-1）阳性细胞、调节性T细胞和巨噬细胞在CRT反应及预后中的意义。
我们使用275例接受新辅助CRT治疗的直肠癌患者的治疗前活检组织，通过免疫组织化学评估肿瘤内及基质中CD8+、PD-1+、FOXP3+、CD68+和CD163+细胞密度。我们确定了这些测量指标对CRT反应和生存的影响。CRT反应通过手术标本的肿瘤退缩分级（TRG）来确定，反应良好者定义为TRG3-4。
反应良好者的肿瘤内CD8+和PD-1+细胞密度显著高于反应不佳者，而反应良好者的基质CD68+细胞密度显著低于反应不佳者。多变量分析显示，肿瘤内高CD8+和PD-1+细胞密度与反应良好者独立相关（CD8：比值比[OR]，2.27；95%置信区间[CI]，1.21 - 4.34，P = 0.010；PD-1：OR，1.97；95%CI，1.03 - 3.84，P = 0.039），且无复发生存期改善（CD8：风险比[HR]，0.56；95%CI，0.32 - 0.98，P = 0.044；PD-1：HR，0.37；95%CI，0.19 - 0.71，P = 0.002）。仅肿瘤内高CD8+细胞密度与总生存期改善相关（P = 0.022）。
治疗前肿瘤内高PD-1+和CD8+细胞密度与CRT反应良好及无复发生存期改善独立相关，肿瘤内高CD8+细胞密度还与总生存期改善相关。这些指标可作为直肠癌的预测和预后生物标志物。
