Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung

Abstract

Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumorcooperating phenotype. High numbers of regulatory T cells, or alternatively expression of Vista on lymphocytes was present. Tumoricidal dendritic cells were absent in tumor tissue, and barely present in bronchoalveolar lavage, whereas tumor-friendly monocytoid and plasmocytoid dendritic cells were seen in both. Alveolar macrophages were predominantly differentiated into tumor-cooperating M2 types, whereas tumoricidal M1 macrophages were absent or rare. The expression of PDL1 on tumor cells did not correlate with any other immune cells. Expression of PD1 on lymphocytes was frequently encountered. None of analyzed immune cells showed correlation with overall survival. Immune cells in bronchoalveolar lavage and tissue did not correlate. For the first time, a tissue-based analysis of different immune cells in squamous cell and adenocarcinomas of the lung is provided, trying to explain their potential role in tumor development and progression. Discordant numbers of cells with bronchoalveolar lavage are most probably due to the fact that bronchoalveolar lavage reflects the situation in the whole lung, where chronic obstructive lung disease and other conditions are present.

VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy

“…Hernandez-Martinez et al verified the report by Espindola that VISTA plays an immunomodulatory role in human NSCLC, thus implicating its potential as a pivotal therapeutic target [27]. Brcic et al found high numbers of regulatory T cells and VISTA expression on lymphocytes in samples of both squamous cell and adenocarcinomas of the lung [28]. In fact, cases with VISTA expression ≥ 10% had significantly higher numbers of Treg cells, indicating the potential influence of VISTA on immunosuppressive cells.…”

Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects

“…The immunohistochemistry was performed on the available tissue samples after surgery following neoadjuvant SBRT-PATHY using antibodies for apoptosis-inducing factor (AIF), CD3, CD4, CD8, CD20, CD56, CD14, CD15, and S100 protein [14] to explore for the activation and modifications within the tumor microenvironment.…”

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

“…Besides, there has been a remarkable association between VISTA expression with EGFR mutation and improved 5-year overall survival (51). In line with this, Brcic et al have shown that VISTA can be overexpressed in the lymphocytes in squamous cells and adenocarcinoma of the lung (71). Furthermore, high VISTA/PSGL1 co-localization has been associated with improved overall survival in non-small cell lung cancer patients (72).…”