ARG1 mRNA Level Is a Promising Prognostic Marker in Head and Neck Squamous Cell Carcinomas

Abstract

Head and neck squamous cell carcinomas (HNSCC) can be induced by smoking or alcohol consumption, but a growing part of cases relate to a persistent high-risk papillomavirus (HPV) infection. Viral etiology has a beneficial impact on the prognosis, which may be explained by a specific immune response. Tumor associated macrophages (TAMs) represent the main immune population of the tumor microenvironment with a controversial influence on the prognosis. In this study, the level, phenotype, and spatial distribution of TAMs were evaluated, and the expression of TAM-associated markers was compared in HPV positive (HPV+) and HPV negative (HPV−) tumors. Seventy-three formalin and embedded in paraffin (FFPE) tumor specimens were examined using multispectral immunohistochemistry for the detection of TAM subpopulations in the tumor parenchyma and stroma. Moreover, the mRNA expression of TAM markers was evaluated using RT-qPCR. Results were compared with respect to tumor etiology, and the prognostic significance was evaluated. In HPV− tumors, we observed more pro-tumorigenic M2 in the stroma and a non-macrophage arginase 1 (ARG1)-expressing population in both compartments. Moreover, higher mRNA expression of M2 markers—cluster of differentiation 163 (CD163), ARG1, and prostaglandin-endoperoxide synthase 2 (PTGS2)—was detected in HPV− patients, and of M1 marker nitric oxide synthase 2 (NOS2) in HPV+ group. The expression of ARG1 mRNA was revealed as a negative prognostic factor for overall survival of HNSCC patients.

Single-cell RNA sequencing reveals TCR+ macrophages in HPV-related head and neck squamous cell carcinoma

“…also found the same phenomenon ( 22 ). Macrophages are multifunctional plastic cells and are easily modulated by factors in the microenvironment which could promote them to polarize into M1 (antitumor type) or M2 type (pro-tumor type) ( 23 ). During tumor progression, macrophages usually transform into M2 type eventually, which may be related to a favorable prognosis of HPV + HNSCC ( 24 ).…”

“…During tumor progression, macrophages usually transform into M2 type eventually, which may be related to a favorable prognosis of HPV + HNSCC ( 24 ). In breast cancer, gastric cancer, rectal cancer, and pancreatic cancer, survival analysis showed that low levels of M2 macrophage infiltration were associated with a better prognosis ( 23 ). Previous studies have shown that HPV + and HPV - HNSCC cell lines could induce macrophage polarization into M1 and M2 types, respectively.…”

“…Barbora et al. also discovered that in comparison to HPV + tumors, HPV - HNSCC was more infiltrated by M2 TAMs ( 23 ). HPV-promoted tumor cells secrete IL-6, thereby increasing radiosensitivity through M1 polarization of macrophages ( 25 ).…”

The Predictive Value of PAK7 Mutation for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Cancer

“…ARG1 (arginase 1) is a biomarker of M2 macrophages and has immunosuppressive and tumorigenic functions ( 44 ). The mRNA level of ARG1 has been demonstrated as an adverse prognostic factor for the OS of head and neck squamous cell carcinoma (HNSCC) patients ( 45 ). Furthermore, the relative expressions of another set of 16 immune-related genes (chemokines/cytolytic activity/immune checkpoints) in the TCGA cohort were investigated, and found that the expression level of CXCL9 increased significantly in the PAK7-MT group ( Figure 4B ) as compared to the PAK7-WT group.…”

The Present and Future of Virology in the Czech Republic—A New Phoenix Made of Ashes?

“…The team focuses on molecular epidemiology of tumor viruses and developed several approaches to characterize the viral etiology of tumors [35][36][37]. Recently, the group is investigating tumor microenvironments with the aim to explain the prognostic advantage of patients with virally induced tumors and evaluate immune prognostic markers as well as therapeutic markers of small inhibitory molecules [38]. Furthermore, the group also develops tools for the analyses of viromes of both animals and humans and studies the interplay between the virome composition and infection of other pathogens on health and disease [39].…”