Immune Phenotype of Peripheral Blood Mononuclear Cells in Patients with High-risk Non-muscle Invasive Bladder Cancer - Expert Commentary

Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate. Although the BCG therapy is recommended as an immune targeting treatment in high-risk NMIBC tumors, the BCG’s role in the eliciting a response by the innate and adaptive immunity is unclear. A recent study by Audenet et al. published recently in the World Journal of Urology, investigated the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with NMIBC treated with intravesical BCG. 

54 blood samples were collected: 19 high-risk NMIBC patients responding to BCG, 19 high-risk NMIBC patients who are BCG refractory and 16 healthy donors (HD). High-risk NMIBC patients received at least a 6-week induction course of intravesical BCG instillations for the first time. 26 of the patients received BCG therapy prior to blood collection. The investigators analyzed PBMC by fluorescence-activated cell sorting (FACS). The study found that NK cells in NMIBC patients were significantly higher than HD. Although PD-1 levels were similar in the NMIBC patients and the HD, PD-1 expression was higher on CD4+ and CD8+ cells in NMIBC patients. The proportions of total circulating T cells, CD4+ and CD8+ were similar in the two groups.

Interestingly, there were no significant difference between the 19 patients who responded to BCG and the 19 patients in the BCG-refractory group. No significant difference was found in the frequency of NK and T cells between the 26 patients who started BCG prior to the blood collection and the12 who did not. The investigators found significant differences between NMIBC patients and HD in the proportion of NK cells, and the expression of Tim-3, TIGIT and PD-1 on CD4+ and CD8+ cells. 

Despite the common use of BCG in the treatment of NMIBC for several decades, the exact immunologic mechanisms of action are not clear.  This study adds suggests that a distinct systemic immune response is present in NMIBC patients treated with BCG.

Written by: Bishoy M. Faltas, MD, Weill Cornell Medicine, New York, NY

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