Advanced stages of cancer often involve multiple tumors in different locations in the body. These tumors are associated with a microenvironment that can influence tumor responses to immunotherapy. Whether tumors and their disparate microenvironment can interact together at distance in a multiple tumor setting, through a form of cross-talk, and affect their responses to immunotherapy has never been described. Our study investigated the cross-talk between two tumors with disparate microenvironments in a mouse model. We demonstrated that immunosuppressive visceral tumors could influence distant subcutaneous (SC) tumors to render them resistant to immunotherapy. We observed distinct modifications in the SC tumor microenvironment following cross-talk with kidney tumors that exhibit a type-2 macrophage-related immunosuppressive microenvironment. Indeed, when a concomitant kidney tumor was present in the mouse, the SC tumors were highly infiltrated with M2 macrophages and had a reduced T cell and NK cell effector immune profile. Finally, blocking the M2-associated chemokine CCL2 or depleting macrophages, significantly improved the effect of immunotherapy on growth of SC tumors in the presence of concomitant kidney tumors. This work emphasizes the potential negative influence that a tumor, with a strong immunosuppressive microenvironment, can exert on distant tumors that would normally be treatment-responsive. This report may lead to a new vision of the prioritization in the treatment of advanced metastatic cancer.

中文翻译：

---

肿瘤之间的串扰会影响对治疗的反应。

癌症晚期通常会在身体的不同位置涉及多个肿瘤。这些肿瘤与可能影响肿瘤对免疫疗法反应的微环境有关。从来没有描述过肿瘤及其不同的微环境是否可以通过串扰的形式在多个肿瘤环境中远距离相互作用，并影响它们对免疫疗法的反应。我们的研究在小鼠模型中研究了具有不同微环境的两个肿瘤之间的串扰。我们证明了免疫抑制性内脏肿瘤可能会影响远处的皮下（SC）肿瘤，使其对免疫疗法产生抵抗力。我们与表现出2型巨噬细胞相关的免疫抑制性微环境的肾脏肿瘤发生串扰后，在SC肿瘤微环境中观察到了明显的修饰。的确，当小鼠中伴有肾脏肿瘤时，SC肿瘤被M2巨噬细胞高度浸润，并且T细胞和NK细胞效应子的免疫特性降低。最后，阻断M2相关的趋化因子CCL2或消耗巨噬细胞，可显着改善免疫疗法对伴有肾肿瘤的SC肿瘤生长的影响。这项工作强调了具有强烈免疫抑制微环境的肿瘤可能对通常具有治疗反应性的远处肿瘤产生潜在的负面影响。该报告可能会导致对治疗晚期转移性癌症的优先次序产生新的看法。阻断与M2相关的趋化因子CCL2或消耗巨噬细胞，可显着提高免疫疗法对伴有肾肿瘤的SC肿瘤生长的影响。这项工作强调了具有强烈免疫抑制性微环境的肿瘤可能对通常具有治疗反应性的远处肿瘤产生潜在的负面影响。该报告可能会导致对治疗晚期转移性癌症的优先次序产生新的看法。阻断与M2相关的趋化因子CCL2或消耗巨噬细胞，可显着提高免疫疗法对伴有肾肿瘤的SC肿瘤生长的影响。这项工作强调了具有强烈免疫抑制性微环境的肿瘤可能对通常具有治疗反应性的远处肿瘤产生潜在的负面影响。该报告可能会导致对治疗晚期转移性癌症的优先次序产生新的看法。可以在通常对治疗有反应的远处肿瘤上发挥作用。该报告可能会导致对治疗晚期转移性癌症的优先次序产生新的看法。可以在通常对治疗有反应的远处肿瘤上发挥作用。该报告可能会导致对治疗晚期转移性癌症的优先次序产生新的看法。