Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer

Microbes Infect. 2024 May-Jun;26(4):105315. doi: 10.1016/j.micinf.2024.105315. Epub 2024 Feb 27.

Abstract

Background: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC.

Methods: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC.

Results: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC.

Conclusions: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

Keywords: Colorectal cancer; HPV; ISM2; Prognosis; Tumor immune microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Proliferation
  • Cohort Studies
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / virology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology
  • Papillomavirus Infections* / immunology
  • Papillomavirus Infections* / virology
  • Prevalence
  • Tumor Microenvironment* / immunology