PUB038 Prognostic Impact of FOXP3-Positive Tumor Infiltrating Lymphocytes in Small-Cell Lung Cancers

Introduction Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. Methods We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

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Weighting tumor-specific TCR repertoires as a classifier to stratify the immunotherapy delivery in non–small cell lung cancers

Science Advances ◽

10.1126/sciadv.abd6971 ◽

2021 ◽

Vol 7 (21) ◽

pp. eabd6971

Author(s):

Jiefei Han ◽

Ruofei Yu ◽

Jianchun Duan ◽

Jin Li ◽

Wei Zhao ◽

...

Keyword(s):

T Cells ◽

Tumor Infiltrating Lymphocytes ◽

Cell Receptor ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancers ◽

Blood Specimens ◽

Complementarity Determining Regions ◽

Index Estimation ◽

Infiltrating Lymphocytes

Analysis of T cell receptor (TCR) repertoires may contribute to better understanding of the response to immunotherapy. By deep sequencing of the TCR β chain complementarity-determining regions in the paired biopsies and peripheral blood specimens of 31 patients with non–small cell lung cancer (NSCLC) treated with anti–programmed death 1 (PD-1) or PD-ligand 1 (PD-L1) therapy, we developed a previously unidentified index, the TCR-based immunotherapy response index (TIR index), that estimated the degree of overlap of the TCR repertoire between tumor-infiltrating lymphocytes and circulating PD-1+CD8+T cells (shared TCR clones). This index correlated with response and survival outcomes of anti–PD-(L)1 treatment. All the TCR sequences of neoantigen-stimulated T cells were included in the shared TCR clones, indicating that TCR clones involved in TIR index estimation represented tumor-specific T cells. Therefore, the TIR index is a feasible approach for assessing tumor-specific TCR and stratifying patients with NSCLC for anti–PD-(L)1 therapy.

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iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer

Cancers ◽

10.3390/cancers12113276 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3276

Author(s):

Alexandra Giatromanolaki ◽

Avgi Tsolou ◽

Eleftheria Daridou ◽

Maria Kouroupi ◽

Katerina Chlichlia ◽

...

Keyword(s):

Immune Response ◽

Overall Survival ◽

Small Cell Lung Carcinoma ◽

Expression Patterns ◽

Tumor Infiltrating Lymphocytes ◽

Small Cell ◽

Small Cell Lung ◽

Tissue Samples ◽

Cell Lung Carcinoma ◽

Infiltrating Lymphocytes

Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs (iNOS+TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of iNOS+TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting iNOS+TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation.

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