Oncolytic adenovirus H101 ameliorate the efficacy of anti‐PD‐1 monotherapy in colorectal cancer

Abstract

Abstract Background Immune checkpoint blockade therapy with anti‐programmed cell death (PD)‐1 antibodies provides therapeutic effect for many patients of various cancers but remains inadequate in colorectal cancer (CRC) patients. The present study aims to assess the efficacy of oncolytic adenovirus (OncoAd) in enhancing the anti‐PD‐1 treatment of CRC. Methods The estimating relative subsets of RNA transcripts algorithm was used for estimating the infiltrated immune cells in melanoma and CRC tissues. The efficacy of OncoAd with anti‐PD‐1 monotherapy was performed in a CT26 CRC mouse model in vivo. Flow cytometric analysis of peripheral blood and tumor tissues determined the difference anti‐tumor immune efficacy of OncoAd with anti‐PD‐1 monotherapy. Results The Cancer Genome Atlas database indicated that CD8+ T cells and regulatory T cells were significantly elevated in melanoma compared to CRC cohorts. Moreover, intratumor injection of oncolytic adenovirus enhanced T cell infiltration and decreased Treg percentages in the CT26 CRC colorectal cancer mouse model. Combinatorial OncoAd with anti‐PD‐1 antibody treatment markedly enhanced the anti‐tumor efficacy of anti‐PD‐1 by significantly decreasing the tumor volume and reducing tumor growth in a CRC mouse model. To the end, OncoAd treatment increased the CD8/Treg ratio, indicating that OncoAd intratumor injection ameliorate the anti‐tumor immune response of anti‐PD‐1 therapy. Conclusion The present study elucidates that OncoAd promotes intratumor T cell infiltration and improves anti‐PD‐1 immunotherapy, thereby providing a potent combinatorial therapeutic strategy for CRC.

Keywords

• anti‐PD‐1 therapy
• CD8+ T cells
• colorectal cancer
• immunotherapy
• oncolytic adenovirus