Distinct tumor-infiltrating lymphocyte landscapes are associated with clinical outcomes in localized non-small cell lung cancer
Menée à partir d'échantillons tumoraux et d'échantillons de tissus adjacents prélevés sur 150 patients atteints d'un cancer du poumon non à petites cellules localisé, cette étude met en évidence une association entre la nature des lymphocytes T ayant infiltré la tumeur et le pronostic
Background : Despite the importance of tumor-infiltrating T lymphocytes (TILs) in cancer biology, the relationship between TIL phenotypes and their prognostic relevance for localized non-small cell lung cancer (NSCLC) has not been well established.
Patients and Methods : Fresh tumor and normal adjacent tissue was prospectively collected from 150 patients with localized NSCLC. Tissue was comprehensively characterized by high-dimensional flow cytometry of TILs integrated with immunogenomic data from multiplex immunofluorescence, TCR sequencing, exome sequencing, RNA sequencing, targeted proteomics, and clinicopathologic features.
Results : While neither the magnitude of TIL infiltration nor specific TIL subsets were significantly prognostic alone, the integration of high-dimensional flow cytometry data identified two major immunotypes (IM1 and IM2) that were predictive of recurrence-free survival independent of clinical characteristics. IM2 was associated with poor prognosis and characterized by the presence of proliferating TILs expressing CD103, PD-1, TIM3, and ICOS. Conversely, IM1 was associated with good prognosis and differentiated by an abundance of CD8+ T cells expressing cytolytic enzymes, CD4+ T cells lacking the expression of inhibitory receptors, and increased levels of B cell infiltrates and tertiary lymphoid structures. While increased B cell infiltration was associated with good prognosis, the best prognosis was observed in patients with tumors exhibiting high levels of both B cells and T cells. These findings were validated in patient tumors from The Cancer Genome Atlas.
Conclusions : Our study suggests that although the number of infiltrating T cells is not associated with patient survival, the nature of the infiltrating T cells, resolved in distinct TIL immunotypes, is prognostically relevant in NSCLC and may inform therapeutic approaches to clinical care.
Annals of Oncology , résumé, 2021