Viral infections and their impact on bladder cancer (BC) immunotherapy
| Virus | Effect on BC immunotherapy | Oncogenic mechanisms | References |
|---|---|---|---|
| Cytomegalovirus (CMV) | May affect immune responses related to cancer, including tumor-promoting inflammation, immune evasion, and immunosuppression | CMV reactivation can recruit T and natural killer (NK) cells to the site of infection, promoting dendritic cell (DC) maturation and increasing the immune response against the tumor | [13, 14, 44, 45] |
| Persistence can lead to T cell senescence, compromising immune effectiveness, especially in the tumor microenvironment (TME) | [44] | ||
| Reactivation in bladder tissue after treatment, including infection of monocytes, fibroblasts, and tumor cells, indicating a complex role in cancer resistance and treatment responses | [45] | ||
| Epstein-Barr virus (EBV) | Potential to enhance immune responses against tumor-associated antigens (TAAs), but also associated with oncogenesis | EBV reactivation can stimulate T cell responses specific to TAAs, but the relationship between EBV and bladder carcinogenesis is not fully understood | [51, 52] |
| In non-invasive muscle urothelial tumors, it was found that poor differentiation was correlated with a high genomic load of the EBV | [52] | ||
| Latency within B cells with potential reactivation under immunosuppression | [50] | ||
| Latent membrane protein 1 (LMP1) protein of EBV can regulate TAAs and stimulate strong CD4+ cytotoxic T lymphocyte (CTL) responses | [51] | ||
| EBV-associated malignancies include nasopharyngeal carcinoma and Hodgkin’s lymphoma | [52] | ||
| Human papillomavirus (HPV) | Rarely involved in the pathogenesis of BC, but some studies suggest occasional involvement. Not directly discussed, but may impact immune modulation due to its oncogenic nature | HPV infection may contribute to tumor formation and affect the immune response to tumor cells, although its specific impact on Bacillus Calmette-Guerin (BCG) immunotherapy is unclear | [34, 36] |
| HPV16 was found in a single case of BC, with no detection of HPV18. Previous research failed to detect HPV DNA in hundreds of bladder tumor samples | [46] | ||
| A 2011 meta-analysis showed that 17% of BC cases were HPV-positive | [49] | ||
| BK polyomavirus (BKPyV) | It can interfere with the effectiveness of BCG treatment | BKPyV reactivation can affect local immunity and contribute to cancer progression, interfering with the effectiveness of BCG treatment, especially in immunocompromised patients | [53] |
| One study detected BKPyV in 1.7% of BC biopsy specimens | [54] | ||
| Possible involvement in early carcinogenesis and aggressive BC behavior | Cell proliferation in urothelial cells through large T antigen (LTag) | [55] | |
| Loss of p53 helicase domain in tumors, selecting for tumor survival | [56] | ||
| Integration of viral and host genomes leads to “super-enhancers” that regulate gene expression, promoting cell cycle progression, DNA repair, and mitosis while downregulating cell adhesion genes | [59] | ||
| Tumors exhibit invasive and high-grade behavior | [60] | ||
| John Cunningham polyomavirus (JCPyV) | Possible oncogenic potential, particularly in the development of BC | Persistent infection in kidneys and urinary tract after initial infection, with continuous oncogenic risk in urothelial cells | [55] |
| Case reported in kidney transplant recipient with high-grade urothelial carcinoma after JCPyV nephropathy | [56] | ||
| Potential for tumor cell transformation | [57] | ||
| Torque Teno virus (TTV) | No direct link to carcinogenesis, but may serve as an indicator of immune competence | Decreased presence in urine of BC patients compared to healthy volunteers | [58, 59] |
| Highly prevalent but non-pathogenic |
