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Tumor infiltrating T cells influence prognosis in stage I–III non-small cell lung cancer.

ABSTRACT: BackgroundT cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4+ T helper cells (Th), CD8+ cytotoxic (Tc) and FOXP3+ regulatory T (Treg) cells in NSCLC, we performed this analysis.MethodsBy counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral Th cells, Treg cells and Tc cells in n=294 NSCLC patients with pTNM stage I–III disease.ResultsStrong CD4+ infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4+ infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio <1 was associated with high grade NSCLC tumors (P=0.020). High CD8+ T cell infiltration was an independent prognostic factor for OS (P=0.040) and progression-free survival (PFS) (P=0.012) in the entire study collective. The OS benefit of high CD8+ infiltration was especially prominent in PD-L1 negative NSCLC (P=0.001) but not in PD-L1 positive tissue (P=0.335). Moreover, positive FOXP3+ expression in tumor infiltrating lymphocytes was associated with increased OS (P=0.007) and PFS (P=0.014) in SCC but not in ADC and LCC (all P>0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236).ConclusionsHigh proportion of CD8+ Tc cells correlated with improved prognostic outcome in stage I–III NSCLC. Th cells and Treg cells have implications on outcome with respect to tumor histology and biology.

SUBMITTER: Schulze AB

PROVIDER: S-EPMC7330340 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Project description:BackgroundLung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III-N2 non-small cell lung cancer (NSCLC).MethodsWe enrolled 1011 patients with pathologically confirmed stage III-N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low-, medium-, and high-risk groups. Overall survival (OS), progression-free survival (PFS), local regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log-rank test.ResultsAbnormal CEA levels were associated with worse five-year OS, PFS and DMFS; abnormal CYFRA21-1 levels were associated with worse five-year OS and LRFS; and abnormal CA125 levels were associated with worse five-year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five-year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001-0.004) among the three risk groups.ConclusionsThe combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: Serum CEA, CYFRA21-1, and CA125 levels can be used as prognostic factors of postoperative N2 non-small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable.What this study addsOur model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists.

Project description:Background: There was rare studies on prognosis of pulmonary venous CTC and early or advanced NSCLC patients. We want to investigate whether CTCs and the subtype of it can predict the prognosis of NSCLC patients. Patients and Methods: One hundred and fourteen patients with stage I-III NSCLC were included CanPatrol™ CTC analysis. PD-L1 expression level were detected in CTC of pulmonary vein. PD-L1, number of CTC in pulmonary, CTC's subtype, clinical characteristics, prognosis of patients were analyzed. Results: 110/114 (96.5%) patients could be found CTCs in pulmonary vein, 58/114 (50.9%) patients had CTC≥15/ml in pulmonary vein, 53/110 patients (48.2%) were defined as having MCTC subtype and 56/110 patient were found have PD-L1 (+) CTC in pulmonary vein. Multivariate analyses showed that PVCTC, MCTC, and stage were independent factors of DFS (P < 0.05). No OS difference was found between number of CTC (P = 0.33) and other CTC factors (P > 0.05), only stage was independent factor of OS (P = 0.019). There were decreases of CTC number and MCTC number in EGFR mutant subgroup (P = 0.0009 and P = 0.007). There were increases of CTC (P = 0.0217), MCTC (P = 0.0041), and PD-L1 (+) CTC (P = 0.0002) number in KRAS mutant subgroup. There was increase of MCTC (P =0.0323) number in BRAF mutant. There were fewer CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0346). There were more PD-L1 positive CTCs in pulmonary vein for patients with ALK rearrangement, KRAS mutant, BRAF mutant, or ROS1 mutant than in patients with full wild-type gene (P = 0.0610, P = 0.0003, P = 0.032, and P = 0.0237). There were more mesenchymal CTCs in pulmonary vein for patients with KRAS mutant and BRAF mutant than in patients with full wild-type gene (P = 0.073 and P = 0.0381). There were fewer mesenchymal CTCs in pulmonary vein for patients with EGFR mutant than in patients with full wild-type gene (P = 0.0898). Conclusions: The patients with high number of CTCs, MCTCs, or PD-L1 (+) CTCs in pulmonary vein experienced poor prognosis of DFS. There are obvious correlations between the CTC subtype of NSCLC and the gene subgroups of tumor tissue.

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Tumor infiltrating T cells influence prognosis in stage I–III non-small cell lung cancer.

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