Dataset related to article "Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer."

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2^pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2^pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2^pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2^pos T cells showing a relative increase of terminally-differentiated CD27^neg/CD45RA^pos (T_EMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on T_EMRA Vδ2^pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2^pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57^pos and T_EMRA Vδ2^pos T cells. Similar results were found for tumor infiltrating Vδ2^pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2^pos T cells by inducing higher frequencies of circulating CD57^pos T_EMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2^pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57^pos T_EMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2^pos T cells.人类γδ T淋巴细胞（gamma delta T cells）是一类非常规先天样淋巴细胞，具备广泛的抗肿瘤活性，在癌症免疫治疗领域具有良好的应用前景。在此背景下，Vδ2^pos T细胞是多种实体瘤免疫治疗方案的优先靶点。然而，衰老与化疗（chemotherapy, CHT）对Vδ2^pos T细胞的影响尚不明确。本研究采用多参数流式细胞术（multi-parametric flow cytometry），对比了结直肠癌肝转移（colorectal liver metastases, CLM）患者外周血及肿瘤浸润性Vδ2^pos T细胞的频率、终末分化状态、衰老情况与效应功能，并以性别、年龄匹配的健康供者作为对照。接受化疗的CLM患者外周血中，Vδ2^pos T细胞数量减少，同时终末分化的CD27阴性/CD45RA阳性（T_EMRA）细胞亚群相对增多。该亚群的富集与衰老标志物CD57的表达上调密切相关。T_EMRA型Vδ2^pos T细胞表面CD57的获得，同时伴随着细胞毒性、肿瘤坏死因子α（tumor necrosis factor-α, TNF-α）及干扰素γ（interferon-γ, IFN-γ）产生能力的损伤。上述特征与接受化疗的CLM患者体内Vδ2^pos T细胞呈现的免疫衰老表型一致，该现象同时伴随共刺激标志物CD28的丢失以及CD16表达的诱导。年龄大于60岁的接受化疗的CLM患者，其体内CD57阳性（CD57^pos）及T_EMRA型Vδ2^pos T细胞的频率更高。从接受化疗的CLM患者肿瘤组织中纯化的肿瘤浸润性Vδ2^pos T细胞亚群，也得到了相似的实验结果。化疗方案的毒性还会影响Vδ2^pos T细胞的稳态：在年龄小于60岁且接受化疗的CLM患者体内，循环CD57阳性T_EMRA细胞亚群的频率显著升高。综合来看，本研究数据表明，CLM患者体内衰老型Vδ2^pos T细胞的富集不仅由患者自身衰老诱导，化疗的毒性作用还会进一步加速功能失调的CD57阳性T_EMRA细胞的积累，这类细胞的抗肿瘤活性存在显著损伤。上述结果对于预测CLM患者的临床结局，以及优化基于非常规Vδ2^pos T细胞的细胞癌症免疫治疗方案均具有重要价值。