Cholera vaccine may improve prognosis in colorectal cancer patients
Administering cholera vaccine following a diagnosis of colorectal cancer (CRC) affords survival benefit, reducing the risks of death from CRC and overall mortality, according to a recent study.
"Our study [provides] preliminary data that cholera vaccine might protect against the progression of CRC, and it might be used as an adjuvant therapy if subsequent randomization clinical trial can support this finding,” said Dr Jianguang Ji, corresponding author of the study and associate professor in Medical Epidemiology at Lund University in Sweden, in an email to MIMS.
In their investigation, Ji and colleagues examined 175 CRC patients (median age at diagnosis 62 years; 51.4 percent female) who were given a prescription for the cholera vaccine after diagnosis and 525 propensity-matched CRC controls who did not receive the vaccine.
Over a mean follow-up of 7 years, 15 patients with postdiagnostic cholera vaccine exposure and 16 controls died as a result of their illness. These numbers corresponded to 12.2 and 19.7 per 1,000 person-years incidence rate of CRC mortality. [Gastroenterology 2017;doi:10.1053/j.gastro.2017.09.009]
On Cox regression analysis, postdiagnostic use of the cholera vaccine showed a protective association with the primary outcome of risk of death due to CRC (adjusted hazard ratio [HR], 0.53; 95 percent CI, 0.29 to 0.99; p=0.04) and the secondary outcome of risk of death overall (adjusted HR, 0.59; 0.37 to 0.94; p=0.02).
Reduced mortality with postdiagnosis cholera vaccination was largely observed, irrespective of patient age, tumour stage at diagnosis and gender.
“However, stratified analyses were not statistically significant because of the limited number of cases,” the authors said.
Inhibiting CRC progression
Cholera vaccine constitutes both killed whole cells of Vibrio cholerae O1 and recombinant cholera toxin B subunit (CTB)—a nontoxic protein that has been recently used together with other antigens to induce immunity against other bacteria, such as Helicobacter pylori and Streptococcus pneumonia. [Appl Microbiol Biotechnol 2012;93:1937-45; PloS One 2011;6:e27102]
In previous studies, cholera toxin has been shown to upregulate immune cell populations and reduce the development of colon polyps, particularly in a mouse model. [Carcinogenesis 2015;36:280-90; Mucosal Immunol 2016;doi:10.1038/mi.2016.95; Nat Rev Gastroenterol Hepatol 2016;13:691-706]
Based on available evidence, the authors postulated that CTB not only protects against cholera infection but also inhibits the progression of CRC by facilitating the recruitment of immune cells (eg, CD8+ T cells, macrophages and NK cells) into tumour tissue and/or by alternating the expression of genes that are related to tumorigenesis.
Further studies, including well-designed cohort studies and randomized clinical trials, are needed to confirm the present findings and elucidate the mechanisms by which cholera vaccine reduces mortality risk, the authors said.
The present study has several limitations. First is the lack of information on some individual-level risk factors, such as medical treatments, smoking status and dietary factors. Second is the uncertainty concerning medical adherence in the cohort, which may have led to the possibility of exposure misclassifications.