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Neoadjuvant Chemotherapy for Bladder Cancer: Focus on Immune Cells in the Tumor Microenvironment

By: Emily Rhode
Posted: Wednesday, November 16, 2022

Xiao-Feng Zhou, MD, of China-Japan Friendship Hospital, Beijing, and colleagues observed that pretreatment tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) after neoadjuvant chemotherapy may not be reliable prognostic indicators of response in patients with muscle-invasive bladder cancer. Specifically, CD68+ and CD68+PD-L1− TAM infiltration levels decreased significantly after neoadjuvant chemotherapy, whereas infiltration levels of CD4+ T cell, CD8+ T cell, or FOXP3+ T regulatory cells experienced no significant changes after neoadjuvant chemotherapy. These findings were published in Cancer Medicine.

“[These] dynamic data suggest that [neoadjuvant chemotherapy] might affect [the tumor microenvironment] through regulating the infiltration level CD68+ and CD68+PD-L1− TAMs,” said the study authors.

The study identified 54 eligible patients with muscle-invasive bladder cancer who had received neoadjuvant chemotherapy from January 2012 to December 2019. Patients were categorized as definite responders (n = 25) or incomplete responders (n = 29), depending on their down-staging in response to treatment. Examinations and blood sampling was performed every 3 months for 2 years after definite treatment and again every 6 months for an additional 3 years. Infiltration levels of CD4+, CD8+, CD68+, FOXP3+, PD-L1+, CD4+FOXP3+, CD4+FOXP3−, CD8+PD-L1+, CD8+PD-L1−, CD68+PD-L1+, and CD68+PD-L1− were analyzed in tumor samples collected from patients before and after neoadjuvant chemotherapy.

Researchers found no significant difference between immune cell infiltration levels at baseline for definite responders and incomplete responders. However, they noted that a tobacco history was associated with worse efficacy with neoadjuvant chemotherapy (hazard ratio = 3.405; P = .038). Infiltration levels of CD68+PD-L1− TAMs experienced a significant post-decrease, whereas levels of CD68+PD-L1+ TAMs had no significant difference. No significant change in infiltration levels was observed in CD4+ T cells, CD8+ T cells, or FOXP3+ T regulatory cells.

Disclosure: The study authors reported no conflicts of interest.

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