Editorial: Infection-Mediated Inflammation Promotes Cancer Initiation and/or Progression

Ibrahim M Sayed ^1,2* Soumita Das ²

• ¹ Assiut University, Assiut, Egypt
• ² Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, USA, Lowell, Massachusetts, United States

Microbial infection mediates the initiation and progression of cancer through several strategies. These strategies include the stimulation of host inflammatory responses (Infection-mediated inflammation), upregulation of oxidative DNA/RNA damage and production of reactive oxygen species (ROS), suppression of host repair mechanisms, and uncontrolled proliferation of host cells (Sayed et al., 2021;Sayed et al., 2020). There are several bacteria that mediate cancer programs via infection-mediated inflammation such as Helicobacter pylori (H.pylori), Fusobacterium nucleatum, Enterotoxigenic B. fragilis, Clostridium difficile, and Enterococcus faecalis (Sayed et al., 2024). H.pylori is a gram-negative bacilli that cause gastric cancer, colon cancer, and extra-intestinal cancers (Sayed et al., 2021). The pathogenesis of H.pylori includes the following pathways; upregulation of inflammatory signaling pathway via NF-κB stimulation, increasing DNA/RNA oxidative damage and inhibiting the host repair pathways, inducing the epithelial cell proliferation and suppression of the tumor suppressor protein P53 (Sayed et al., 2021). In this issue, two studies discussed the pathogenesis of H.pylori infection. Elbehiry et al. described the role of H.pylori virulence factors in bacterial pathogenesis including outer membrane proteins (OMPs), enzymes (such as catalase and urease), and toxins (such as vacuolating cytotoxin gene (vacA) and cytotoxin-associated gene A (cagA)) (Elbehiry et al., 2025). Bawali et al. reported the role of extracellular vesicle connection in driving inflammation and gastrointestinal tract cancers (Bawali et al., 2024). The outer membrane vesicles (OMVs) of H. pylori and host-cell-derived extracellular vesicles (EVs) mediate the transport of carcinogenic cytotoxin of H. pylori, the cytotoxin-associated gene A (CagA).CagA diminishes the host immune response, induces inflammation in the gastric mucosa by stimulating IL-8 and nuclear factor-κB (NF-κB), and upregulates the reactive oxygen species (ROS) generation. EVs released by infected cells contain CagA, reach systemic circulation, and deliver the oncogenic factors to the distal parts of the body. The OMVs of H. pylori induce extra gastric disease such as hepatic fibrosis by affecting the exosomes in liver cells and stimulating hepatic satellite cells. Also, the fusion of H. pylori OMVs with other microbial OMVs, which is PhD-dependent, can be an oncogenic factor for extra gastric cancers. The authors conclude that the advancement of EV research and bioengineering and OMV-OMV fusion could be efficient therapeutic targets (Bawali et al., 2024). Regarding the development of effective vaccine against H. pylori infection, Elbehiry et al. described several vaccine approaches which are developed for H.pylori including inactivated whole-cell vaccines, genetically modified protein-based subunit vaccines, cagA antigen as a vaccine candidate, multiepitope DNA vaccines, and vector (carrier) vaccines. However, the efficacy of several vaccine types is unknown and most of the research findings are preliminary. The OMP-vaccine is safer and more effective in reducing antibiotic resistance. Toxin vaccines have some degree of safety but challenge the selection process. Current clinical trials assess recombinant vaccines incorporating various antigens such as the cagA, vacA, ure, babA, sabA, oipA, and porin proteins. The ideal vaccine against H.pylori should involve the immune-suppressing mechanisms and the selection of effective antigens and adjuvants. Besides, testing the potential candidate vaccines should be performed in a suitable animal model before human clinical trials.Immune cells play critical roles in the development of oral cancer. Lymphocytes and macrophages are the main players in anti-tumor immunity. Shifting from CD8 + T cells into CD4 + T cells and cytokine profile have been linked to cancer progression (Caponio et al., 2023). The cytokines that enhance tumor microenvironment include PGE-2, TGF-β and IL-10 (Caponio et al., 2023). Chronic infection and crosstalk between the immune cells and neural cells could promote oral cancers. In this issue, D'Silva et al. Not only bacteria, but also viruses play a role in cancer development. Viruses such as Hepatitis B virus, Hepatitis C virus, Epstein Barr virus, and Human papillomavirus are reported with several human cancers as liver cancer, Burkitt's lymphoma, and cervical cancer. There are several strategies of virusinduced cancers such as activation of oncogenes, downregulation of tumor suppressor proteins, alteration of cellular signaling and immune response, promotion of inflammatory responses, mediating DNA damage, and inducing host cell proliferation (Ameya & Birri, 2023). In this issue, Javadi et al.assessed the correlation between human papillomavirus (HPV) infection and colorectal cancer (Javadi et al., 2024). In a cross-section study including forty CRC biopsies, twenty-six samples were positive for HPV DNA. HPV was also detected in the urine of HPV-positive patients (14/26, 53.8%). Genotyping analysis revealed that HPV16 was the most common subtype in CRC biopsies and urine samples, with no significant difference between genders. HPV45 and HPV83 were detected in CRC biopsies of male and female patients respectively. HPV31 and HPV56 were also detected in the urine of male and female patients respectively. The authors also assessed HPV16 E6 and E7 oncoproteins in exosomes from serum samples, suggesting the potential of a non-invasive method in HPV diagnosis. The authors concluded the role of HPV infection in CRC development and the impact of HPV DNA screening in CRC tissues on patients' survival (Javadi et al., 2024).Infections can cause death among leukemic patients due to weakened immune systems. In this issue, Although the infection rate of NTM is very low (0.02%), the death rate was high. It is crucial to consider NTM in leukemia patients with early AFB cultures and prescribe the appropriate therapies, especially in case of disseminated infection including neutropenic fevers, abnormal pulmonary nodules, or unusual skin lesions.In conclusion: Bacterial and viral infections contribute to cancer development through different approaches including inflammation, DNA damage, and induction of cancer signaling pathways.Understanding the infection-mediated cancer programs will help in the development of effective therapeutic interventions and/or preventive vaccine approaches.