Tumor microenvironment crosstalk in mCRC
How would you propose to decipher the crosstalk between tumor-stromal-immune cells that initiate and perpetuate immune suppressive tumor microenvironment of metastatic colorectal cancer?
Kang Liu
Senior Principal Scientist
Boehringer Ingelheim
Call for proposals: All incoming answers will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial research funding of up to 200,000 euros will be available for proposals that will receive support by our review team.
More information
Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women each year in the United States. Metastasis is the major cause of death in patients with CRC and is often associated with resistance to immunotherapy.
The growth of tumor cells depends on its soil, the tumor microenvironment (TME). In the TME, the stromal cells including cancer associated fibroblast cells (CAFs) crosstalk to tumor cells and immune cells and may form multi-cellular hubs that drive cancer stemness and immune escape1. The mechanisms that orchestrate and maintain this crosstalk in the metastatic CRC TME are potentially actionable drug targets to enable novel therapies. The challenge to identify and validate molecular targets in the metastatic CRC TME has been: 1) an incomplete understanding of the cellular and molecular mechanisms underlying the crosstalk between tumor-stromal-immune cells causing immune-suppressive TME in the metastatic CRC, and 2) proper models to screen and validate immune-suppressive stromal and CAF targets are lacking.
We seek human in vitro translational and in vivo models that faithfully recapitulate aspects of the immune suppressive TME of metastatic CRC (defined in vivo models, cell line 2 or 3D, explant, etc.) to help identify new potential therapeutic targets (such as genes, proteins, or pathways). Eventually these models should enable testing and characterizing therapeutic strategies in reverting immune suppression of the TME in patients to prevent metastasis and improve immunity against colorectal cancers.
- Innovative and translational in vitro systems or in vivo models that recapitulate the TME of metastatic CRC in human to allow the identification and validation of targets that sustain and mediate an immunosuppressive TME, thereby enabling immune activation and suppressing tumor growth.
- Covering, but not limited to:
- in vitro culture using primary immune cells and tumor cell lines (2D or 3D) or primary material that recapitulate human metastasis CRC TME and tumor-stromal-immune cell crosstalk for the identification of potential starting points (genes, proteins, pathways) for new therapies.
- in vivo screens using an in vivo model of metastatic CRC with translational value.
Applications containing preliminary evidence and characterization of the initiation and perpetuation of immune suppressive TME of metastatic CRC and applications containing human translational models will be prioritized.
The following will be considered out of scope:
- in vitro and in vivo models in which CRC metastasis is not reproducible, poorly characterized or without demonstrated relevance/link to human biology or only unique or specific to nonhuman species.
- Proposals without any preliminary/supporting data
- Proposals that are considered primarily fee for service
If your project is selected, you will have the opportunity to directly collaborate with the Cancer Immunology and Immune Modulation Discovery Research team of Boehringer Ingelheim. You can expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestones and does not exceed 200,000 euros per submitted project in total.
The opportunity for a funded stay at Boehringer Ingelheim for technology exchange / training is potentially available, as is the availability of custom biological tools and reagents.
Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).
To maintain the highest degree possible in an open innovation environment, we plan to announce the winner(s) publicly and feature them on opnMe.com and our social media channels. We would guide you through this process and as part of it we would kindly ask for your upfront consent, in case our scientific jury had selected your answer.
We are seeking research collaboration proposals that contain:
- A well-structured proposal outlining a new and compelling scientific approach.
- Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing techniques and established assays.
- Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 200,000 euros per submitted project in total.
- Proven track record in the required field of expertise.
- Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a laboratory.
Applications containing preliminary evidence and characterization of the initiation and perpetuation of an immune suppressive TME of metastatic CRC and applications containing human translational models will be prioritized.
Please use our answer submission template to provide a 2-3 page non-confidential proposal (available for download here).
If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.
We are currently seeking answers for the following scientific challenge: How would you propose to decipher the crosstalk between tumor-stromal-immune cells that initiate and perpetuate immune suppressive tumor microenvironment of metastatic colorectal cancer?
All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for each selected proposal.
We can only accept research proposals if they arrive by the submission deadline on December 20, 2022, 11.59 pm PST.
Spatially organized multicellular immune hubs in human colorectal cancer
Pelka K., Hofree M., Chen J. H., Sarkizova S., Pirl J. D., Jorgji V., Bejnood A., Dionne D., Ge W. H., Xu K. H., Chao S. X., Zollinger D. R., Lieb D. J., Reeves J. W., Fuhrman C. A., Hoang M. L., Delorey T., Nguyen L. T., Waldman J., Klapholz M., Wakiro I., Cohen O., Albers J., Smillie C. S., Cuoco M. S., Wu J., Su M-J., Yeung J., Vijaykumar B., Magnuson A. M., Asinovski N., Moll T., Goder-Reiser M. N., Applebaum A. S., Brais L. K., DelloStritto L. K., Denning S. L., Phillips S. T., Hill E. K., Meehan J. K., Frederick D. T., Sharova T., Kanodia A., Todres E. Z., Jané-Valbuena J., Biton M., Izar B., Lambden C. D., Clancy T. E., Bleday R., Melnitchouk N., Irani J., Kunitake H., Berger D. L., Srivastava A., Hornick J. L., Ogino S., Rotem A., Vigneau S., Johnson B. E., Corcoran R. B., Sharpe A. H., Kuchroo V. K., Ng K., Giannakis M., Nieman L. T., Boland G. M., Aguirre A. J., Anderson A. C., Rozenblatt-Rosen O., Regev A., Hacohen N.
Cell 2021, 184(18):4734-4752.e20.
