Berntsson Jonna, Svensson Maria C, Leandersson Karin, Nodin Björn, Micke Patrick, Larsson Anna H, Eberhard Jakob, Jirström Karin
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
Cancer Immunology, Department of Translational Medicine, Lund University, Sweden.
Int J Cancer. 2017 Oct 15;141(8):1654-1666. doi: 10.1002/ijc.30869. Epub 2017 Jul 20.
Accumulating evidence demonstrates an association between dense infiltration of lymphocytes and prognosis in colorectal cancer (CRC), but whether this prognostic impact differs by tumour location remains unknown. This study investigated the prognostic impact of cytotoxic and regulatory T cells in CRC, with particular reference to the anatomical subsite of the primary tumour. The density of CD3 , CD8 and FoxP3 tumour-infiltrating T cells was calculated in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of high and low lymphocyte density on 5-year overall survival, in subgroup analysis of right colon, left colon and rectum. High CD8 cell density was a favourable prognostic factor for patients with right-sided colon tumours (hazard ratio [HR]=0.53, 95% confidence interval [CI] 0.29-0.95), independent of age, sex, TNM stage, differentiation grade and vascular invasion, with a significant prognostic interaction between CD8 cells and right-sidedness (p = 0.031). High FoxP3 cell density was an independent favourable prognostic factor only in patients with rectal tumours (HR = 0.54, 95% CI 0.30-0.99), and CD3 cell density was an independent favourable prognostic factor for tumours in the right colon and rectum, but there was no significant prognostic interaction between CD3 or FoxP3 cells and sidedness. These results demonstrate that the prognostic impact of tumour-infiltrating lymphocytes in CRC differs by primary tumour site, further indicating that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.
越来越多的证据表明，淋巴细胞的密集浸润与结直肠癌（CRC）的预后之间存在关联，但这种预后影响是否因肿瘤位置而异仍不清楚。本研究调查了细胞毒性T细胞和调节性T细胞在CRC中的预后影响，特别参考了原发性肿瘤的解剖亚部位。在来自一个基于人群的前瞻性队列的557例新发CRC病例的组织微阵列中计算了CD3、CD8和FoxP3肿瘤浸润T细胞的密度。应用Kaplan-Meier和Cox回归分析来确定高、低淋巴细胞密度对5年总生存率的影响，并对右半结肠、左半结肠和直肠进行亚组分析。高CD8细胞密度是右侧结肠肿瘤患者的有利预后因素（风险比[HR]=0.53，95%置信区间[CI]0.29-0.95），独立于年龄、性别、TNM分期、分化程度和血管侵犯，且CD8细胞与右侧肿瘤之间存在显著的预后相互作用（p=0.031）。高FoxP3细胞密度仅是直肠肿瘤患者的独立有利预后因素（HR=0.54，95%CI 0.30-0.99），而CD3细胞密度是右半结肠和直肠肿瘤的独立有利预后因素，但CD3或FoxP3细胞与肿瘤部位之间没有显著的预后相互作用。这些结果表明，CRC中肿瘤浸润淋巴细胞的预后影响因原发性肿瘤部位而异，进一步表明肿瘤位置可能是治疗决策（包括免疫治疗资格）中需要考虑的重要因素。
