The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.

Front Immunol

Laboratory for Molecular and Cellular Therapy (LMCT), Translational Oncology Research Center (TORC), Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.

Published: August 2024

AI Article Synopsis

  • Advanced lung cancer patients show limited responses to immunotherapy, highlighting the importance of finding reliable biomarkers and targets to improve treatment decisions and effectiveness.
  • Factors like PD-L1 expression and tumor mutation burden are linked to better responses, but the role of tumor-infiltrating myeloid cells (TIMs) remains unclear due to their diversity.
  • Research indicates that the interaction between lung cancer and the bone marrow environment is crucial, yet the exact influences of bone marrow on tumor behavior in solid cancers need further investigation to identify new treatment strategies.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324509PMC
http://dx.doi.org/10.3389/fimmu.2024.1397469DOI Listing

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