肿瘤浸润淋巴细胞过继转移（TIL 疗法）已被证明对于治疗实体癌（包括非小细胞肺癌 (NSCLC)）非常有效。然而，由于尚不清楚的原因，并非所有患者都能从这种疗法中受益。因此，定义与自体 TIL 产品的高肿瘤反应性相关的标记物是实现更好的定制免疫疗法的关键。我们质疑免疫细胞浸润的组成是否与扩增的 TIL 产品的肿瘤反应性相关。对 26 个早期和 20 个晚期 NSCLC 肿瘤病灶的免疫细胞浸润进行无偏流式细胞术分析，用于与 T 细胞分化和激活状态以及生成的 TIL 产物的扩增率和抗肿瘤反应相关。患者之间肿瘤免疫浸润的组成差异很大。 Spearman 等级相关性显示，高 B 细胞浸润与患者扩增的 TIL 产物的肿瘤反应性呈负相关，如暴露于自体肿瘤消化物时细胞因子的产生所定义的。深入分析显示，B细胞浸润​​较高的肿瘤病灶含有三级淋巴结构（TLS）相关的免疫浸润，包括分泌BCL6抗体的B细胞、IgD BCL6 B细胞和CXCR5 BLC6 CD4 T细胞，以及较高比例的初始CD8 T细胞。总之，NSCLC 肿瘤中免疫细胞浸润的组成与扩增的 TIL 产品的功能相关。因此，我们的研究结果可能有助于改善 TIL 治疗的患者选择。© 2024 作者。经泰勒许可出版

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies. We questioned whether the composition of immune cell infiltrates correlated with the tumor-reactivity of expanded TIL products. Unbiased flow cytometry analysis of immune cell infiltrates of 26 early-stage and 20 late-stage NSCLC tumor lesions was used for correlations with the T cell differentiation and activation status, and with the expansion rate and anti-tumor response of generated TIL products. The composition of tumor immune infiltrates was highly variable between patients. Spearman's Rank Correlation revealed that high B cell infiltration negatively correlated with the tumor-reactivity of the patient's expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. In-depth analysis revealed that tumor lesions with high B cell infiltrates contained tertiary lymphoid structure (TLS)-related immune infiltrates, including BCL6+ antibody-secreting B cells, IgD+BCL6+ B cells and CXCR5+BLC6+ CD4+ T cells, and higher percentages of naïve CD8+ T cells. In conclusion, the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of the expanded TIL product. Our findings may thus help improve patient selection for TIL therapy.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.