Augmented interferon regulatory factor 7 axis in whole tumor cell vaccines prevents tumor recurrence by inducing interferon gamma-secreting B cells

ABSTRACT

Among cancer immunotherapy, which has received great attention in recent years, cancer vaccines can potentially prevent recurrent tumors by using the exquisite power and specificity of the immune system. Specifically, whole tumor cell vaccines (WTCVs) based on surgically resected tumors have been considered to elicit robust anti-tumor immune responses by exposing various tumor-associated antigens to host immunity. However, most tumors have little immunogenicity because of immunoediting by continuous interactions with host immunity; thus, preparing WTCVs based on patient-derived non-modified tumors cannot prevent tumor onset. Hence, the immunogenicity of tumor cells must be improved for effective WTCVs. In this study, we indicate the importance of the interferon regulatory factor 7 (Irf7) axis, including Irf7 and its downstream factors, within tumor cells in regulating immunogenicity. Indeed, WTCVs that augmented the Irf7 axis have exerted remarkable recurrence-preventive effects when vaccinated after tumor inactivation by radiation. Most notably, vaccination with murine colon cancer cells that enhanced the Irf7 axis prevented the development of challenged tumors in all mice and resulted in a 100% survival rate during the observation period. Furthermore, the mechanism leading to vaccine effectiveness was mediated by interferon-gamma-producing B cells. This study provides novel insights into how to enhance tumor immunogenicity and use WTCVs as recurrence prophylaxis.

KEYWORDS:

• B cell
• IFNγ
• Irf7
• vaccine
• whole tumor cell vaccine

Acknowledgments

The authors thank Ms. Rei Okabe, Ms. Nanami Eguchi, Ms. Chie Kusama, and Ms. Ayano Yamauchi for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

NK, KS, and HW designed the study. NK, HW, YT, and RT performed experiments. All authors analyzed data and discussed the results. NK, KS, and HW contributed to manuscript preparation. All authors approved the final version of this manuscript for publication.

Data availability statement

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2213132.

Additional information

Funding

This work was partly supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#22K19449, K. Seino, #18K07286, H. Wada), Joint Research Program of the Institute for Genetic Medicine (K. Seino), the project of junior scientist promotion (K. Seino), the Photo-excitonix Project in Hokkaido University (K. Seino), GSK Japan Research Grant 2021 (H. Wada), JST SPRING (#JPMJSP2119, N. Kajihara), and JSPS KAKENHI (#22J21076, N. Kajihara).