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.
OBJECTIVES
We described patients with microscopic residual disease (R1) operated on for non-small-cell lung cancer (NSCLC) and investigated predictive factors for R1. We also examined prognostic factors for overall survival in these patients.
METHODS
From June 2003 to December 2019, a total of 2595 patients benefited from an anatomical resection operation for NSCLC in our department. All preoperative data were prospectively collected in Epithor, the French thoracic surgery national database. All pre-, per- and postoperative care followed the current recommendations. Tumours were classified by experienced pathologists according to the TNM classification and the resection status R. Survival information was collected retrospectively using the French national death register.
RESULTS
A total of 94 R1 patients (3.6%) and 2255 R0 patients (86.9%) were identified. R1 patients showed significant differences: They were older (p = 0.02), with a high rate of pneumonectomy(p < 0.001), more squamous cell carcinomas (p < 0.001) and more cases of advanced-stage disease (p < 0.001). We proved that incomplete resection was a poor and independent prognostic factor whereas complete resection had a significant impact on overall survival (HR: 4.66 [3.46–6.27]). Thus, we identified high clinical T status (odds ratio [OR]: 8.82 [5.00–15.56]), high clinical N status (OR: 3.54 [2.13–5.87), squamous cell carcinoma (OR: 3.86 [2.33–6.42]), obesity (OR 1.91 [1.04–3.52]) and low forced expiratory volume in 1 s (OR: 3.62 [1.70–7.68]) as risk factors for R1. No statistical differences were found according to the location of positive resection margin or treatment, whether adjuvant or neoadjuvant.
CONCLUSIONS
Incomplete resection was a poor prognostic factor for overall survival of patients operated on for NSCLC, particularly in the advanced stages of the disease. Identification of different predictive factors should help to avoid this situation.
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