scholarly journals Analysis of Intra-Tumoral Macrophages and T Cells in Non-Small Cell Lung Cancer (NSCLC) Indicates a Role for Immune Checkpoint and CD200-CD200R Interactions

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1788
Author(s):  
Anders Tøndell ◽  
Yashwanth Subbannayya ◽  
Sissel Gyrid Freim Wahl ◽  
Arnar Flatberg ◽  
Sveinung Sørhaug ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Expression Profiles ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Cell Immune Response ◽  
Small Cell Lung ◽  
Tumor Associated Macrophages ◽  
Cell Lung Carcinoma

Non-small cell lung carcinoma (NSCLC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths. Immunotherapy with immune checkpoint inhibitors shows beneficial responses, but only in a proportion of patients. To improve immunotherapy in NSCLC, we need to map the immune checkpoints that contribute immunosuppression in NSCLC-associated immune cells and to identify novel pathways that regulate immunosuppression. Here, we investigated the gene expression profiles of intra-tumoral immune cells isolated from NSCLC patients and compared them to the expression profiles of their counterparts in adjacent healthy tissue. Transcriptome analysis was performed on macrophages, CD4+ and CD8+ T cells. The data was subjected to Gene Ontology (GO) term enrichment and weighted correlation network analysis in order to identify mediators of immunosuppression in the tumor microenvironment in NSCLC. Immune cells from NSCLC revealed a consistent differential expression of genes involved in interactions between myeloid cells and lymphocytes. We further identified several immunosuppressive molecules and pathways that may be activated in tumor-associated macrophages in NSCLC. Importantly, we report novel data on immune cell expression of the newly described CD200/CD200R1 pathway, and the leukocyte immunoglobulin-like receptors (LILRs), which may represent novel innate immune checkpoints, dampening the anti-tumor T cell immune response in NSCLC. Our study substantiates the importance of tumor-associated macrophages as a mediator of immunosuppression and a promising target for immunotherapy.

Prognostic value of peripheral naive CD8+ T cells in oligometastatic non-small-cell lung cancer

2021 ◽  
Author(s):  
Xin Zhao ◽  
Yan Zhang ◽  
Zhenlin Gao ◽  
Yaguang Han
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

scholarly journals In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Lygia Bertalha Yaegashi ◽  
Camila Machado Baldavira ◽  
Tabatha Gutierrez Prieto ◽  
Juliana Machado-Rugolo ◽  
Ana Paula Pereira Velosa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cox Regression ◽  
Cytotoxic T Cells ◽  
Small Cell ◽  
Malignant Cells ◽  
Pathological Stage ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors’ immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8+, Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers—the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III > 24.89 fibers/mm². Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression > 52.86 cells/mm² and CD3+ ≤ 278.5 cells/mm². We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.

scholarly journals A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma

2021 ◽  
pp. LMT47
Author(s):  
Jerónimo Rafael Rodríguez-Cid ◽  
Sonia Carrasco-Cara Chards ◽  
Iván Romarico González-Espinoza ◽  
Vanessa García-Montes ◽  
Julio César Garibay-Díaz ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Objective Response ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
Total Study Population ◽  
Cell Lung Carcinoma

Background: Immunotherapy has demonstrated an improved overall survival (OS) and progression-free survival (PFS) as second-line treatment and subsequent lines compared with chemotherapy.  Materials and methods: This was a retrospective review among eight medical centers comprising 100 patients with a confirmed diagnosis of non-small-cell lung carcinoma, in their second-line treatment or beyond with immune checkpoints inhibitors treatment. The current study aimed to analyze effectiveness of immunotherapy in second-line treatment or further in the Mexican population, using PFS rate, OS rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. Results: In total, 100 patients met the criteria for enrollment in the current study. From the total study population, 49 patients (49.0%) were male and 51 (51.0%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the study. A total of 61 patients (61.0%) had partial response; 11 (11.0%) stable disease; 2 (2.0%), complete response, 4 (4.0%), progression; and 22 (22.0%) were nonevaluable. We found a median PFS of 4 months (95% CI: 3.2–4.7 months) and an OS of 9 months (95% CI: 7.2–10.7 months). Conclusion: The response to immunotherapy is similar, with an improvement in OS and PFS, independent of which drug is used. Patients using nivolumab had a better survival, although that was not statistically significant.

scholarly journals Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma

2018 ◽  
Vol 10 (2) ◽  
pp. 198-202 ◽  
Author(s):  
Phatcharawat Chirasuthat ◽  
Pamela Chayavichitsilp
Keyword(s):  
Case Report ◽  
Immune Checkpoint ◽  
Small Cell Lung Carcinoma ◽  
Maculopapular Rash ◽  
Small Cell ◽  
Stevens Johnson Syndrome ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Johnson Syndrome ◽  
Inpatient Settings

Atezolizumab is a humanized anti-PD-L1 immune checkpoint antibody that is currently used in many kinds of advanced carcinoma including metastatic non-small cell lung cancer. The cutaneous side effect profile reported only 20% of the patients which had only mild maculopapular rash that required no treatment. There is no case report of anti-PD-L1 antibody-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) eruptions. To the best of our knowledge, there is no case report of atezolizumab-induced SJS or SJS/TEN induced by anti-PD-L1 immune checkpoint antibodies. We believe that our report will be useful to dermatologists who are consultants in the inpatient settings, as atezolizumab is an anti-neoplastic agent that has a potential to be used in multiple malignancies.

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