# Transcutaneous Imiquimod Combined With Anti‐Programmed Cell Death‐1 Monoclonal Antibody Extends the Survival of Mice Bearing Renal Cell Carcinoma

## TL;DR

Combining imiquimod cream and anti-PD-1 antibody treatment significantly improves survival in mice with kidney cancer by boosting immune response.

## Contribution

Demonstrates that combining transcutaneous imiquimod with anti-PD-1 therapy enhances antitumor immunity in renal cell carcinoma.

## Key findings

- Combination therapy significantly suppressed tumor growth and prolonged mouse survival.
- The treatment increased RENCA tumor-specific IgG and altered CD8+ T cell subsets in the spleen.
- A negative correlation between tumor and spleen weights was observed in IQM-treated mice.

## Abstract

Imiquimod (IQM), an imidazoquinoline derivative, is an immunomodulator that activates an adaptive immune response. IQM is applied topically for genital warts and actinic keratosis. Programmed cell death‐1 (PD‐1) suppresses activated T cells by binding to programmed cell death‐ligand 1 and programmed cell death‐ligand 2, braking antitumor immunity. Anti‐PD‐1 therapy has been used for various malignant neoplasms including renal cell carcinoma (RCC). Whether combination therapy with transcutaneous administration of IQM cream and intraperitoneal administration of anti‐PD‐1 monoclonal antibody (mAb) suppresses mouse RCC cells growing in subcutaneous tissue was investigated.

Female BALB/c mice were implanted subcutaneously with 2 × 105 RENCA mouse RCC cells and treated with a transcutaneously applied cream containing IQM and intraperitoneal administration of anti‐PD‐1 mAb beginning 5 days after cell implantation. Tumor burden and survival of the mice were determined. RENCA tumor‐specific IgG production and a minor CD8+ T cell subset derived from the spleen of the mice bearing RENCA tumor were detected by flow cytometry. The tumor and spleen weights of mice treated with IQM, anti‐PD‐1 mAb, and their combination were compared.

Combination therapy with IQM and anti‐PD‐1 mAb significantly suppressed tumor growth compared to each monotherapy and prolonged the survival of the mice. The combination therapy produced more RENCA tumor‐specific IgG than either IQM or anti‐PD‐1 mAb alone. The percentage of the CD44highCD62Llow CD8+ T cell subset (effector memory T cells) among splenocytes from mice treated with IQM therapy increased. The CD44lowCD62Llow CD8+ T cell subset (pre‐effector‐like T cells) of mice treated with anti‐PD‐1 mAb increased. A negative correlation between tumor and spleen weights was suggested in mice treated with therapies containing IQM.

The present results show that combination therapy with IQM and anti‐PD‐1 mAb might be a promising novel therapeutic strategy for advanced RCC.