The Emerging Role of CD8(+) Tissue Resident Memory T (T(RM)) Cells in Antitumor Immunity: A Unique Functional Contribution of the CD103 Integrin.
The Emerging Role of CD8(+) Tissue Resident Memory T (T(RM)) Cells in Antitumor Immunity: A Unique Functional Contribution of the CD103 Integrin.
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DOI：
10.3389/fimmu.2018.01904
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发表时间：
2018
影响因子：
7.3
通讯作者：
Mami-Chouaib F
中科院分区：
文献类型：
--
作者：
Corgnac S;Boutet M;Kfoury M;Naltet C;Mami-Chouaib F
肿瘤免疫治疗的目的是刺激肿瘤特异性细胞毒性T淋巴细胞及其随后的运输，使其到达并坚持肿瘤微环境，识别和消除恶性靶细胞。因此，表征浸润人实体瘤的CD8+ T淋巴细胞的表型和效应功能，对于更好地理解和操纵局部抗肿瘤免疫反应，以及确定它们对当前癌症免疫治疗方法成功的贡献至关重要。越来越多的证据表明，大量的CD3+CD8+肿瘤浸润淋巴细胞亚群是组织常驻记忆T （TRM）细胞，并且正在作为激活的肿瘤特异性T细胞亚群出现。这些TRM细胞聚集在各种人类癌症组织中，包括非小细胞肺癌（NSCLC）、卵巢癌和乳腺癌，并通过表达CD103 [αE(CD103)β7]和/或CD49a [α1(CD49a)β1]整合素以及c型凝集素CD69来定义，这很可能是它们驻留特征的原因。CD103与上皮细胞标志物E-cadherin结合，从而促进上皮肿瘤胰岛中TRM细胞的保留和细胞毒性免疫突触与特异性癌细胞的成熟，导致t细胞受体（TCR）依赖性靶细胞杀伤。此外，CD103整合素触发与TCR信号合作的双向信号事件，使t细胞迁移和最佳细胞因子产生。值得注意的是，浸润人类NSCLC肿瘤的TRM细胞也表达抑制受体，如程序性细胞死亡-1，用阻断抗体中和这些受体，增强cd103依赖性tcr介导的对自体癌细胞的细胞毒性。因此，TRM细胞在肿瘤部位的积累解释了更有利的临床结果，并可能与部分癌症患者免疫检查点阻断的成功有关。
Cancer immunotherapy is aimed at stimulating tumor-specific cytotoxic T lymphocytes and their subsequent trafficking so that they may reach, and persist in, the tumor microenvironment, recognizing and eliminating malignant target cells. Thus, characterization of the phenotype and effector functions of CD8+ T lymphocytes infiltrating human solid tumors is essential for better understanding and manipulating the local antitumor immune response, and for defining their contribution to the success of current cancer immunotherapy approaches. Accumulating evidence indicates that a substantial subpopulation of CD3+CD8+ tumor-infiltrating lymphocytes are tissue resident memory T (TRM) cells, and is emerging as an activated tumor-specific T-cell subset. These TRM cells accumulate in various human cancer tissues, including non-small-cell lung carcinoma (NSCLC), ovarian and breast cancers, and are defined by expression of CD103 [αE(CD103)β7] and/or CD49a [α1(CD49a)β1] integrins, along with C-type lectin CD69, which most likely contribute to their residency characteristic. CD103 binds to the epithelial cell marker E-cadherin, thereby promoting retention of TRM cells in epithelial tumor islets and maturation of cytotoxic immune synapse with specific cancer cells, resulting in T-cell receptor (TCR)-dependent target cell killing. Moreover, CD103 integrin triggers bidirectional signaling events that cooperate with TCR signals to enable T-cell migration and optimal cytokine production. Remarkably, TRM cells infiltrating human NSCLC tumors also express inhibitory receptors such as programmed cell death-1, the neutralization of which, with blocking antibodies, enhances CD103-dependent TCR-mediated cytotoxicity toward autologous cancer cells. Thus, accumulation of TRM cells at the tumor site explains the more favorable clinical outcome, and might be associated with the success of immune checkpoint blockade in a fraction of cancer patients.
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