在晚期肺癌患者中观察到的对免疫治疗的适度反应率强调需要确定可靠的生物标志物和靶标，从而增强治疗决策和疗效。 PD-L1 表达、肿瘤突变负担以及效应 T 细胞浸润增强的“热”肿瘤微环境等因素一直与阳性反应相关。相比之下，大量存在的肿瘤浸润性骨髓细胞（TIM）部分的预测作用仍然有些不确定，部分原因是它们在个体发育、表型、位置和功能方面的巨大多样性。然而，大量临床前和临床研究确定了肺癌进展与髓内和髓外造血改变之间的明确联系，导致紧急骨髓生成，但以巨核细胞/红细胞和淋巴分化为代价。这些观察结果证实，肺癌等实体癌和骨髓生态位 (BMN) 之间必定会发生持续的串扰。然而，BMN（包括造血干细胞和祖细胞、分化的免疫细胞和基质细胞）在实体癌患者中的研究仍未充分。随后，对于肿瘤安装的造血干扰线索的确切范围及其对免疫治疗的预测能力尚未达成明确的共识。当前的单细胞组学时代正在重塑我们对造血过程和肺 TIM 亚簇景观的理解，我们的目标是对携带实体癌的受试者的 BMN 内 TIM 的分层分化过程提供最新的概述。我们的全面概述强调，肺癌应被视为一种全身性疾病，其中控制肺肿瘤-BMN 串扰的线索可能会支持新生物标志物和药物靶标的定义，从而有可能减轻 NSCLC 领先免疫疗法的高损耗率。版权所有 © 2024 卡尔德隆-埃斯皮诺萨、德里德、伯努特、詹森、范霍纳克、赫斯特曼斯、德贝克尔、范里特、德科斯特和戈瓦特。

Modest response rates to immunotherapy observed in advanced lung cancer patients underscore the need to identify reliable biomarkers and targets, enhancing both treatment decision-making and efficacy. Factors such as PD-L1 expression, tumor mutation burden, and a 'hot' tumor microenvironment with heightened effector T cell infiltration have consistently been associated with positive responses. In contrast, the predictive role of the abundantly present tumor-infiltrating myeloid cell (TIMs) fraction remains somewhat uncertain, partly explained by their towering variety in terms of ontogeny, phenotype, location, and function. Nevertheless, numerous preclinical and clinical studies established a clear link between lung cancer progression and alterations in intra- and extramedullary hematopoiesis, leading to emergency myelopoiesis at the expense of megakaryocyte/erythroid and lymphoid differentiation. These observations affirm that a continuous crosstalk between solid cancers such as lung cancer and the bone marrow niche (BMN) must take place. However, the BMN, encompassing hematopoietic stem and progenitor cells, differentiated immune and stromal cells, remains inadequately explored in solid cancer patients. Subsequently, no clear consensus has been reached on the exact breadth of tumor installed hematopoiesis perturbing cues nor their predictive power for immunotherapy. As the current era of single-cell omics is reshaping our understanding of the hematopoietic process and the subcluster landscape of lung TIMs, we aim to present an updated overview of the hierarchical differentiation process of TIMs within the BMN of solid cancer bearing subjects. Our comprehensive overview underscores that lung cancer should be regarded as a systemic disease in which the cues governing the lung tumor-BMN crosstalk might bolster the definition of new biomarkers and druggable targets, potentially mitigating the high attrition rate of leading immunotherapies for NSCLC.Copyright © 2024 Calderon-Espinosa, De Ridder, Benoot, Jansen, Vanhonacker, Heestermans, De Becker, Van Riet, Decoster and Goyvaerts.