PDF(Pubmed)
Abstract：
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.
摘要：
在晚期肺癌患者中观察到的免疫疗法的适度反应率强调了确定可靠的生物标志物和靶标的必要性。提高治疗决策和疗效。PD-L1表达等因素，肿瘤突变负荷，和具有增加的效应T细胞浸润的热肿瘤微环境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）分数的预测作用仍然有些不确定，部分原因是它们在个体发育方面的高耸多样性，表型,location,和功能。然而，许多临床前和临床研究建立了肺癌进展与髓内和髓外造血改变之间的明确联系，导致以巨核细胞/红系和淋巴样分化为代价的紧急骨髓生成。这些观察结果证实，必须在诸如肺癌之类的实体癌和骨髓生态位（BMN）之间发生连续的串扰。然而,BMN,包括造血干细胞和祖细胞，分化的免疫和基质细胞，在实体癌患者中仍未充分探索。随后，对于肿瘤植入的造血干扰信号的确切广度及其对免疫疗法的预测能力，尚未达成明确共识。随着当前的单细胞组学时代正在重塑我们对造血过程和肺TIM子集群景观的理解，我们的目的是提供有关实体癌患者BMN内TIM分级分化过程的最新概述。我们的全面概述强调，肺癌应被视为一种全身性疾病，在这种疾病中，控制肺部肿瘤-BMN串扰的线索可能会支持新的生物标志物和药物靶标的定义。有可能减轻NSCLC主要免疫疗法的高流失率。
