Classical Hodgkin Lymphoma (CHL) is unusually sensitive to PD1 inhibition and PDL1 is highly expressed on CHL cells and in the tumor microenvironment. This could be interpreted as evidence of exhaustion, but paradoxically, PD1+ lymphocyte infiltration does not predict PD1 inhibitor response and no increase in cytotoxic markers is seen after PD1 therapy as might be expected with reversal of exhaustion. In contrast to PD1, elevated PDL1 does predict response to PD1 inhibitors and recent data associate both retained CHL MHC-II expression and increased T helper (TH) T-cell receptor diversity with response suggesting a connection to the TH compartment. We performed a phenotypic, spatial and functional assessment of T cell exhaustion in CHL and found lower PD1 expression and exhaustion marker co-expression in CHL as compared to reactive nodes and similar proliferative and cytokine production capacity. We found no correlation between PDL1 expression and exhaustion signatures. Instead, we identified a strong association between PDL1 expression and CHL MHC-II expression, TH recruitment, and enrichment of Th1 regulatory cells. These data suggest that a dominant effect of PDL1 expression in CHL may be T helper engagement and promotion of regulatory microenvironment rather than maintenance of exhaustion.

中文翻译：

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PDL1 塑造经典霍奇金淋巴瘤微环境，而不诱导 T 细胞耗竭。

经典霍奇金淋巴瘤 (CHL) 对 PD1 抑制异常敏感，并且 PDL1 在 CHL 细胞和肿瘤微环境中高表达。这可以解释为疲惫的证据，但矛盾的是，PD1+淋巴细胞浸润并不能预测PD1抑制剂的反应，并且PD1治疗后没有观察到细胞毒性标记物的增加，这与疲惫逆转所预期的一样。与 PD1 相比，升高的 PDL1 确实可以预测对 PD1 抑制剂的反应，并且最近的数据将保留的 CHL MHC-II 表达和增加的 T 辅助 (TH) T 细胞受体多样性与表明与 TH 区室相关的反应相关联。我们进行了表型分析，对 CHL 中 T 细胞耗竭的空间和功能评估发现，与反应性节点相比，CHL 中 PD1 表达和耗竭标记物共表达较低，并且具有相似的增殖和细胞因子产生能力。我们发现 PDL1 表达和耗竭特征之间没有相关性。相反，我们发现 PDL1 表达与 CHL MHC-II 表达、TH 募集和 Th1 调节细胞富集之间存在很强的关联。这些数据表明，CHL 中 PDL1 表达的主要作用可能是 T 辅助细胞参与和促进调节微环境，而不是维持耗竭。TH 募集和 Th1 调节细胞的富集。这些数据表明，CHL 中 PDL1 表达的主要作用可能是 T 辅助细胞参与和促进调节微环境，而不是维持耗竭。TH 募集和 Th1 调节细胞的富集。这些数据表明，CHL 中 PDL1 表达的主要作用可能是 T 辅助细胞参与和促进调节微环境，而不是维持耗竭。