The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer
The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer
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DOI：
10.1158/1078-0432.ccr-16-2047
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发表时间：
2017-07-15
影响因子：
11.5
通讯作者：
Spagnoli, Giulio C.
中科院分区：
文献类型：
--
作者：
Governa, Valeria;Trella, Emanuele;Spagnoli, Giulio C.
目的：不同T淋巴细胞亚群的肿瘤浸润与结直肠癌的良好预后相关。先天免疫系统的作用仍在争论中。我们研究了结直肠癌浸润性CD 66 b（+）中性粒细胞的临床相关性、表型和功能特征以及它们与CD 8（+）T细胞的相互作用。实验设计：在包括> 650个可评估的结直肠癌样本的组织微阵列上通过IHC分析CD 66 b（+）和CD 8（+）细胞浸润。通过流式细胞术评估组织浸润和外周血CD 66 b（+）细胞的表型特征。结果：结直肠癌组织中CD 66 b（+）细胞浸润与生存率显著相关。有趣的是，在结直肠癌中，中性粒细胞经常与CD 8（+）T细胞共定位。功能研究表明，尽管中性粒细胞缺乏直接抗肿瘤潜力，但与外周血或肿瘤相关中性粒细胞（TAN）共培养可增强次优浓度抗CD 3 mAb诱导的CD 8（+）T细胞活化、增殖和细胞因子释放。此外，在最佳活化条件下，在CD 66 b（+）细胞存在下的CD 8（+）细胞刺激导致表达CD 45 RO/CD 62 L“中央记忆”表型的细胞数量增加。重要的是，与单独的CD 8（+）T细胞浸润相比，CD 66 b（+）和CD 8（+）T淋巴细胞联合肿瘤浸润与显著更好的预后相关。因此，中性粒细胞浸润增强了CD 8（+）T细胞浸润的结直肠癌预后意义，表明它们可能有效地促进抗肿瘤免疫。(C)2017年AACR。
Purpose: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b(+) neutrophils and their crosstalk with CD8(+) T cells.Experimental Design: CD66b(+) and CD8(+) cell infiltration was analyzed by IHC on a tissue microarray including > 650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b(+) cells were evaluated by flow cytometry. CD66b(+)/CD8(+) cells crosstalk was investigated by in vitro experiments.Results: CD66b(+) cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8(+) T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8(+) T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8(+) cell stimulation in the presence of CD66b(+) cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b(+) and CD8(+) T lymphocytes is associated with significantly better prognosis, as compared with CD8(+) T-cell infiltration alone.Conclusions: Neutrophils enhance the responsiveness of CD8(+) T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8(+) T cells, suggesting that they might effectively promote antitumor immunity. (C) 2017 AACR.