# Targeting the IL-33/ST2 Pathway in Colorectal Cancer Immunotherapy

> **NIH NIH K99** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $118,721

## Abstract

Summary/Abstract:
I am a postdoctoral fellow at Indiana University who has developed a unique set of skills in tumor immunology
and cancer immunotherapy. Throughout my graduate and postdoctoral studies, I established a productive track-
record with seven first/co-first author manuscripts and a total of 18 top-tier peer-reviewed research and review
papers, including: Nature Nanotechnology, ACS Nano, Nature Communications, The Journal of Clinical
Investigation, Cancer Immunology Research and JCI Insight. Furthermore, I am listed as co-inventor on several
patent applications.
Development/Training: My long-term goal is to establish myself as an independent researcher with the focus
on cancer immunotherapy. Throughout the years, my research became unique in the immunotherapy field as I
am bridging multiple disciplines. This unique skill set requires in-depth knowledge in immunology and
immunotherapy as well as solid understanding in bioinformatics, nanotechnology and the biomedical engineering
field. The K99/R00 award will help in achieving my goal, as I will be guided towards becoming an independent
investigator under the guidance of extremely well-established scientists such as Dr. Xiongbin Lu (cancer biology)
and Dr. Sophie Paczesny (immunology and immunotherapy). I will also closely collaborate with Dr. Chi Zhang
(bioinformatics deconvolution) and Dr. Kenneth Dunn (CODEX® Technology and microscopy).
Research: Despite unprecedented clinical tumor regression observed with checkpoint immunotherapy in
colorectal cancer (CRC) patients harboring microsatellite instability high (MSI-H) tumors, a large proportion of
patients receive little to no improvement. Thus, additional checkpoint inhibitors (CPI) in new pathways are
needed; investigation of tumor microenvironment (TME) cell infiltrates and soluble factors will shed light on
possible targets as well as potential pitfalls to such immunotherapies. In this proposal, I will determine the role
of the interleukin-33 (IL-33) and its receptor STimulation 2 (ST2) in CRC immunotherapy. In my JCI Insight
published preliminary data, I established that ST2 expressing tumor associated macrophages (TAMs) hamper
CD8+ T-cell responses. I therefore hypothesize that ST2 expressing TAMs play an essential role in suppressing
antigen-specific T-cell mediated immune responses and that targeting these TAMs could serve as a potential
novel immune checkpoint pathway. Moreover, I will also investigate the role of ST2 on CRC tumor cells and the
contribution of activating the IL-33/ST2 pathway leading to cancer immunotherapy resistance. Finally, I will
assess the translational potential of IL-33/ST2 therapeutic blockade using the IL-33-trap fusion protein to trap
free local and systemic IL-33 or as an alternative approach a ST2 small molecule inhibitor that will block the
functional binding of IL-33 to its ST2 receptor complex, and these agents in combination with other checkpoint
immunotherapy. Support through this award will g...

## Key facts

- **NIH application ID:** 10366086
- **Project number:** 5K99CA248846-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** KEVIN VAN DER JEUGHT
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $118,721
- **Award type:** 5
- **Project period:** 2021-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366086

## Citation

> US National Institutes of Health, RePORTER application 10366086, Targeting the IL-33/ST2 Pathway in Colorectal Cancer Immunotherapy (5K99CA248846-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10366086. Licensed CC0.

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