PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients.
PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients.
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PD-1( ) CD8( ) T 细胞在肿瘤中被耗尽，并在结直肠癌患者的淋巴结引流中发挥作用。
DOI：
10.1038/bjc.2014.416
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发表时间：
2014-09-23
影响因子：
8.8
通讯作者：
Wang, S.
中科院分区：
文献类型：
--
作者：
Wu, X.;Zhang, H.;Xing, Q.;Cui, J.;Li, J.;Li, Y.;Tan, Y.;Wang, S.
阻断PD-1-PD-L1通路是几种晚期癌症的有效治疗策略。但PD-1-PD-L1通路在结直肠癌（CRC）患者中的免疫调节作用尚不清楚。本研究旨在评估PD-1-PD-L1通路在结直肠癌患者肿瘤引流淋巴结（TDLNs）和肿瘤中CD8+ t细胞功能中的作用。流式细胞术检测PD-1在CD8+ T细胞中的表达，免疫组织化学检测PD-L1在tdln和肿瘤组织中的表达。细胞内染色检测CD8+ T细胞中IFN-γ、IL-2的产生及颗粒酶B、穿孔素的表达。PD-1在tdln和肿瘤中CD8+ T细胞上的表达与外周血相比明显上调。表达pd -1的CD8+ T细胞能够在无肿瘤淋巴结（tfln）中产生细胞因子（IL-2和IFN-γ）和穿孔素，但在肿瘤中表现出耗尽表型。此外，PD-L1在肿瘤中而不是tfln中高表达，这与肿瘤浸润性PD-1+ CD8+ T细胞IFN-γ产生受损密切相关。我们的研究结果表明，PD-1对肿瘤中的CD8+ t细胞功能有抑制作用，但对tfln没有抑制作用。
The blockade of PD-1–PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1–PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1–PD-L1 pathway in CD8+ T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients. PD-1 expression on CD8+ T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8+ T cells were detected by intracellular staining. PD-1 expression is markedly upregulated on CD8+ T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8+ T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1+ CD8+ T cells. Our findings suggest a suppressive effect of PD-1 on CD8+ T-cell function in tumours, but not in TFLNs.
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影响因子：
8.4
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
DOI：
10.1073/pnas.0406351101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Thompson, RH;Gillettt, MD;Kwon, ED
通讯作者：
Kwon, ED
影响因子：
5.4
作者：
Urbani, Simona;Amadei, Barbara;Ferrari, Carlo
通讯作者：
Ferrari, Carlo
影响因子：
11.5
作者：
Ohigashi, Y;Sho, M;Nakajima, Y
通讯作者：
Nakajima, Y
影响因子：
11.5
作者：
Thompson, R. Houston;Dong, Haidong;Kwon, Eugene D.
通讯作者：
Kwon, Eugene D.