The efficacy of cancer immunotherapy may be improved by increasing the number of circulating tumor-reactive T cells. The bone marrow is a priming site and reservoir for such T cells. The characteristics of bone marrow-derived tumor-reactive T cells are poorly understood in patients with non-small-cell lung cancer (NSCLC). To compare the responsiveness of tumor antigen-reactive T cells from the bone marrow with matched peripheral blood samples in patients with resectable NSCLC, we used flow cytometry, cytokine capture assays and enzyme-linked immunospot assays to examine the responsiveness of T cells to 14 tumor antigens in matched bone marrow and peripheral blood samples from patients with resectable NSCLC or benign tumors and tumor-free patients. T cells with reactivity to tumor antigens were detected in the bone marrow of 20 of 39 (51%) NSCLC patients. The panel of tumor antigens recognized by bone marrow-derived T cells was distinct from that recognized by peripheral blood-derived T cells in NSCLC patients. Unlike for peripheral blood T cells, the presence of tumor-reactive T cells in the bone marrow did not correlate with recurrence-free survival after curative intent resection of NSCLC. T cells with reactivity to tumor antigens are common in the bone marrow of patients with NSCLC. Tumor-reactive T cells of the bone marrow have the potential to significantly broaden the total repertoire of tumor-reactive T cells in the body. To clarify the role of tumor-reactive T cells of the bone marrow in T cell-based immunotherapy approaches, clinical studies are needed (ClinicalTrials.gov: NCT02515760).

中文翻译：

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骨髓可扩展可切除非小细胞肺癌患者靶向肿瘤相关抗原的功能性T细胞库

通过增加循环的肿瘤反应性T细胞的数量，可以提高癌症免疫疗法的疗效。骨髓是这类T细胞的引发部位和贮藏处。非小细胞肺癌（NSCLC）患者对骨髓源性肿瘤反应性T细胞的特征了解甚少。为了比较可切除的NSCLC患者骨髓中的肿瘤抗原反应性T细胞与匹配的外周血样本的反应性，我们使用流式细胞仪，细胞因子捕获测定法和酶联免疫斑点测定法检查了T细胞对14种肿瘤的反应性可切除的NSCLC或良性肿瘤患者和无肿瘤患者的匹配的骨髓和外周血样本中的抗原。在39名（51％）非小细胞肺癌患者中，有20名在骨髓中发现了对肿瘤抗原具有反应性的T细胞。在非小细胞肺癌患者中，骨髓来源的T细胞识别的肿瘤抗原不同于外周血来源的T细胞识别的肿瘤抗原。与外周血T细胞不同，骨髓中肿瘤反应性T细胞的存在与根治性切除NSCLC后的无复发生存无关。对肿瘤抗原具有反应性的T细胞在NSCLC患者的骨髓中很常见。骨髓的肿瘤反应性T细胞具有显着拓宽体内肿瘤反应性T细胞总库的潜力。为了阐明骨髓中的肿瘤反应性T细胞在基于T细胞的免疫治疗方法中的作用，需要进行临床研究（ClinicalTrials.gov：