Immune Microenvironment and Immunotherapeutic Management in Virus-Associated Digestive System Tumors

Abstract

The development of cancer is a multifactorial phenomenon, while it constitutes a major global health problem. Viruses are an important factor that is involved in tumorigenesis and is associated with 12.1% of all cancer cases. Major examples of oncogenic viruses which are closely associated with the digestive system are HBV, HCV, EBV, HPV, JCV, and CMV. EBV, HPV, JCV, and CMV directly cause oncogenesis by expressing oncogenic proteins that are encoded in their genome. In contrast, HBV and HCV are correlated indirectly with carcinogenesis by causing chronic inflammation in the infected organs. In addition, the tumor microenvironment contains various immune cells, endothelial cells, and fibroblasts, as well as several growth factors, cytokines, and other tumor-secreted molecules that play a key role in tumor growth, progression, and migration, while they are closely interrelated with the virus. The presence of T-regulatory and B-regulatory cells in the tumor microenvironment plays an important role in the anti-tumor immune reaction. The tumor immune microenvironments differ in each type of cancer and depend on viral infection. The alterations in the immune microenvironment caused by viruses are also reflected in the effectiveness of immunotherapy. The present review aims at shedding light on the association between viruses and digestive system malignancies, the characteristics of the tumor immune microenvironment that develop, and the possible treatments that can be administered.

The role of fungi in the diagnosis of colorectal cancer

“…Some researchers have linked Epstein-Barr virus (EBV) to stomach cancer (Zheng et al 2022 ; Noh et al 2023 ). Moreover, several viruses have been described in the context of CRC, such as EBV, human tumour virus (HPV), John Cunningham virus (JCV), and bacteriophages (Marongiu and Allgayer 2022 ; Sarantis et al 2022 ).…”

A systematic review on the molecular and clinical association between Human Papillomavirus and Human Immunodeficiency Virus co‐infection in Head, Neck and Oral squamous cell carcinoma

“…The severity of HPV is classified as low‐risk and high‐risk HPV. High‐risk variants are capable of causing malignancies among which HPV 16,18, 31, and 56 are a few widely analysed genotypes 5,6 …”

“…High-risk variants are capable of causing malignancies among which HPV 16,18,31, and 56 are a few widely analysed genotypes. 5,6 Most HPV-un-associated HNC occurs in the oral cavity and larynx and is primarily associated with tobacco and alcohol use. 7 HPV primarily affects the inner surface of squamous cells and cutaneous tissues and induces warts.…”

Molecular Diagnostics, Pathology and Biomarkers of Gastrointestinal Neoplasms

“…Sarantis et al [ 18 ] investigated the immune microenvironment and immunotherapeutic management of digestive cancers. They proposed assessing the role of viruses in the development of these cancers, as viruses are present in 12% of all malignancies.…”

“…They hypothesized that optimal immunotherapy should be multimodal and inhibit tumor cell proliferation and the immune microenvironment. To enable this, immune checkpoint inhibitors should be combined with vaccines against immunogens and adoptive cell therapy [ 18 ]. Chung et al proposed the simultaneous therapeutic inhibition of PD-L1 and its triggers based on the interaction of PD-L1 with genes that regulate the tumor microenvironment, such as Chemokine (C-X-C motif) ligand 9 (CXCL9) [ 7 ].…”