Abstract
Simple SummaryDuring the fight against tumor, some cells of the immune system such as cytotoxic lymphocytes eliminate tumoral cells while others such as tumor-associated macrophages favor tumor development. Mast cells (MCs) are multifaceted immune cells whose role in cancer is still poorly understood. Moreover, MCs are poorly characterized in the context of cancer and their presence in the tumor microenvironment has been reported to be either associated with good or bad prognosis. In this pilot study we characterized tumor-associated MCs (TAMCs) in lung cancer. We showed that TAMCs exhibited a typical phenotype and can be classified in two subsets according to alphaE integrin (CD103) expression. CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103− counterpart. This study revealed that a high frequency of total TAMC correlated with better overall survival and progression free survival in patients and underlined MC heterogeneity in cancer.Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). However, MCs have been only barely characterized in studies focusing on global immune infiltrate phenotyping. Consequently, their role in cancer is still poorly understood. Furthermore, their prognosis value is confusing since MCs have been associated with good and bad (or both) prognosis depending on the cancer type. In this pilot study performed on a surgical cohort of 48 patients with Non-Small Cell Lung Cancer (NSCLC), we characterized MC population within the TME and in matching non-lesional lung areas, by multicolor flow cytometry and confocal microscopy. Our results showed that tumor-associated MCs (TAMCs) harbor a distinct phenotype as compared with MCs present in non-lesional counterpart of the lung. Moreover, we found two TAMCs subsets based on the expression of CD103 (also named alphaE integrin). CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103− counterpart. In spite of these characteristics, we did not observe a prognosis advantage of a high frequency of CD103+ TAMCs, while a high frequency of total TAMC correlated with better overall survival and progression free survival. Together, this study reveals that TAMCs constitute a heterogeneous population and indicates that MC subsets should be considered for patients’ stratification and management in future research.
Highlights
Non-small cell lung cancer (NSCLC) counts for about 85% of lung cancers and remains the leading cause of cancer-related death worldwide with only 17% of patients alive 5 years after diagnosis [1–3]
We described tumor-associated MCs (TAMCs) heterogeneity and identified two TAMC subpopulations according to their CD103 expression
We found that most TAMCs were located at less than 100 μm of CD31+ endothelial cells, suggesting that TAMCs keep this strategic positioning in the tumor microenvironment (TME) (Figure 2F,G)
Summary
Non-small cell lung cancer (NSCLC) counts for about 85% of lung cancers and remains the leading cause of cancer-related death worldwide with only 17% of patients alive 5 years after diagnosis [1–3]. MCs arise from mast cell progenitors originating from the bone marrow that infiltrate tissues thanks to Vascular Cell Adhesion Molecule-1 (VCAM-1) expressed by endothelial cells and tissue chemotactic factors such as Stem Cell Factor (SCF) On their side, MC progenitors express α4β7 integrins allowing them to bind VCAM-1 and infiltrate lungs where they terminate their differentiation [12,13]. In NSCLC, MC role is controversial [18–21] Of their prognostic impact, MCs are endowed with several immune functions that can influence the TME. Their potential role in cancer is of high interest as highlighted by an increasing number of reviews discussing the topic [14–16]. We described TAMC heterogeneity and identified two TAMC subpopulations according to their CD103 (integrin alpha-E) expression
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