Relationship of Dendritic Cell Density, HMGB1 Expression, and Tumor-infiltrating Lymphocytes in Non–Small Cell Lung Carcinomas

Abstract

Lung cancer is the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) is the most common type of lung carcinomas. In adenocarcinomas, the most frequent histologic type of NSCLC, dendritic cells (DCs) are localized in close contact with tumor cells, and tumor-infiltrating lymphocytes (TILs) are observed in the peritumoral zones. In NSCLC, no studies investigating the density of intratumoral DCs and their impact on the density of TILs have been performed. In addition, the role of the alarmin high-mobility group box1 (HMGB1) in intratumoral DCs recruitment has not been analyzed. In the present study, a total of 82 cases of advanced stages of NSCLC were included. Tissue samples were obtained from biopsies and autopsies. DCs in biopsies or combinations of DCs and NK cells, CD3 T lymphocytes, or CD8 T lymphocytes from autopsy specimens were quantified in high power fields. Also, distribution of HMGB1 in tumor cells was detected. In lung adenocarcinomas, irrespective of subclassification, high densities of infiltrating DCs directly associated to high densities of peritumoral TILs. A 2.5-fold increase in TILs was found in specimens with high densities of infiltrating DCs compared with TILs from adenocarcinomas with low densities of infiltrating DCs. High densities of infiltrating DCs were associated with lung adenocarcinomas expressing cytoplasmic or nuclear-cytoplasmic HMGB1. Our results suggest that in adenocarcinoma patients, HMGB1 produced by tumor cells recruits DCs, which associate to an increase of TILs. Encouraging tumor-DCs-T lymphocytes interactions should improve the quality of life and survival of NSCLC patients.

Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy

“…This transition is associated with the surface expression of stress-associated markers such as calreticulin (CRT) on injured cells, which induce active phagocytosis by myeloid dendritic cells (mDCs) and promote antigen processing and cross-presentation (2). Furthermore, the release into the TME of high-motility group box 1 (HMGB1) protein, a danger-associated molecular pattern (DAMP) molecule, triggers the innate immune response (3, 4). Despite these immune-activating processes, tumor-infiltrating mDCs are likely to be suppressed by factors within the TME (5), and phagocytosis of necrotic cells may not be a sufficient stimulus for optimal cross-presentation of tumor antigens by tumor DCs to trigger protective cytotoxic T cell responses.…”

Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

“…The mechanisms of colorectal carcinogenesis have been extensively described [1, 3–5, 21]. The two major types of genomic instability found in colorectal cancers are chromosomal instability (CIN) and microsatellite instability (MSI).…”

“…Lynch syndrome and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are due to inherited mutations in one of the mismatch repair genes (including MLH1 , MSH2 , and PMS2 ). MMR mutations are found in approximately the remaining 15% of sporadic CRC [1, 3]. In the CpG island methylator phenotype, a number of genes become transcriptionally silenced because of hypermethylation of their promoters, and this represents a key epigenetic mechanism of inactivation of tumor suppressor genes, including certain DNA repair genes [1].…”

“…CRC is a heterogeneous disease regarding tumor localization and genetic and racial differences, and multiple interactions with environmental factors, diet, and style of life influence its development. CRC risk factors include hereditary components (i.e., hereditary nonpolyposis colorectal cancer), predisposal to polyp formation, large bowel inflammatory diseases, obesity, high fat diet, alcoholism, smoking, and stress [1–5]. The use of biomarkers to predict the risk for CRC or the existence of early stages of the tumor could contribute to decreasing the development of the disease and allowing early intervention.…”

Noise Stress Induces an Epidermal Growth Factor Receptor/Xeroderma Pigmentosum–A Response in the Auditory Nerve

“…15,32,33 Briefly, the double IHC procedure produces three reaction products (brown, blue, and black to blackish-blue) in the same tissue sections. For instance, a section that was initially treated with the XPA antibody and developed with DAB exhibited a brown reaction product.…”