Comprehensive T cell repertoire characterization of non-small cell lung cancer

Abstract

Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including nonsmall cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

“…These results are in line with the observation that CD8 + TIL infiltrates correlate with better OS in BTC patients [37,38]. The highest infiltration with CD8 + TIL has been linked to a higher tumor mutational burden (TMB) in solid cancers [39,40], and despite the fact that CCA is not a highly mutated cancer, such as lung cancer or melanoma [41], several tumor-associated antigen (TAA)-derived epitopes were identified as candidate epitopes for immunotherapy [42].…”

Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient

“…Furthermore, tumor with high PD-L1 demonstrated high T cell density and clonality; in addition, TMB was correlated to high T cell clonality. Indeed, EGFR mutant NSCLC presented a lower T cell clonality, that could be a possible explanation of the lower activity of ICIs in these patients [104]. T-cell clone analyses are recently considered as useful for early diagnoses of IrAEs (Immune-related Adverse Events).…”

The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors

“…In M-NSCLC, both spatial and temporal heterogeneity are considered as a main indicators of tumor diversity (65)(66)(67). The spatial type of ITH is related to discrepancies between different regions within the same tumor and may be detected at genetic and immunological level leading to a heterogeneous immune response in distinct populations of cancer cells (65,66,(68)(69)(70). The expression of PD-1 or PD-L1 might vary considerably from region to region within the same tumor, as a result of somatically acquired genetic differences.…”

“…Low PD-L1 expression in brain metastases may be related to the immune sanctuary features of this site (65,67), whereas, bone tissues have a small pool of effective cytotoxic immune cells and a relatively large accumulation of suppressor immune cells (65,74). This immune imbalance may favor the development of bone metastases with less selective pressure from the immune system, making PD-L1 expression in bone metastases less important for immune escape (65,69,74). On the other hand, liver and adrenal glands are immunologically equipped for effective tumor surveillance with potent cytotoxic T-cells and, therefore, they require inhibitory mechanisms, like upregulation of PD-L1 expression, for cancer cells to survive (65,69,73).…”