Role of TLR5 in tumor immune evasion
Using suitable models, how would you propose to validate the role of TLR5 in cancer immune evasion associated with chronic inflammation?
Sudesh Pawaria
Sr Principal Scientist
Oncology Research
Jie Dai
Director
Oncology Research
Call for proposals: 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 based on mutually agreed funding terms.
More information
Acute inflammation supports anti-tumor immunity by activating myeloid cells and T cells. In contrast, chronic inflammation not only promotes tumor initiation, progression, and metastasis, but also facilitates immune evasion and therapy resistance in the tumor microenvironment, largely driven by activation of pattern recognition receptors (PRRs) on myeloid cells and inflammatory mediators such as IL-6, IL-1β, TNF-α, and IFNα 1. The therapeutic potential of inhibiting these receptors or cytokines to improve anti-tumor immune response is emerging but not yet fully explored due to lack of suitable systems to model chronic inflammation. Establishment of in vitro and ex vivo human/mouse models of chronic inflammation can allow evaluation of the role of known inflammatory markers as well as screening and identification of new therapeutic targets.
TLR5 is a well characterized PRR and has a dual role in cancer: acute TLR5 activation can enhance innate immune functions, long-term anti-tumor memory T cell responses and responses to immunotherapy 2, whereas chronic TLR5 signaling may impair dendritic cell differentiation, promote immunosuppressive myeloid subsets, and reduce CD8+ T cell function, ultimately limiting the efficacy of checkpoint therapies 3. Inhibition of TLR5 has been shown in preclinical models to reduce tumor growth and may help overcome immune resistance in selected patient populations 4. However, there are currently no active clinical or preclinical TLR5 inhibitor programs in oncology indications.
Developing in vitro and ex vivo human and mouse models of chronic inflammation is essential to clarify the tumor-promoting mechanisms associated with TLR5 and to identify patient populations that may benefit from TLR5 inhibition. These models will also facilitate the discovery of new inflammatory markers and therapeutic targets.
We invite proposals to develop or apply models that define the role of chronic inflammation—specifically TLR5 activation and inhibition—in cancer progression and immune evasion and to discriminate from any acute immune enhancing activity function. Selected projects may receive access to custom TLR5 antagonists and direct collaboration with the Oncology Research Team.
Proposals that can define the immune settings that determine the role of TLR5-driven inflammation in the seemingly opposing directions. This can be achieved by using
- Immune cell-based models of chronic inflammation (myeloid cells/T cells/tumor cells)
- Human and mouse in vitro and ex vivo models
- Syngeneic and humanized in vivo tumor models
- in silico models
- Non-mouse; non-human models
If your project is selected, you will have the opportunity to directly collaborate with the Oncology Research Team of Boehringer Ingelheim.
As an incentive specific to this opn2EXPERTS call, we offer exclusive access to custom biological tools and reagents, in particular well-characterized TLR5 antagonists, from our research activities to validate your submitted hypotheses, should your proposal be selected by our scientific review team. In addition, you can also 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 300,000 Euros per submitted project in total (including direct, indirect, overhead costs).
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).
Our scientific review will address the following key success criteria for selecting winning proposals:
The objective of the proposed solution must be to understand and validate the role of TLR5 activation in opposing immune context (tumor preventing vs tumor promoting). It must be based on a compelling scientific hypothesis and address the in-scope and out-of-scope criteria of this call.
Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing and established models.
Ideally, the proposed solution is backed up by relevant (preliminary) data, and it should be based on established and existing methods, assays and involve tools, reagents, or data that are accessible.
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 does not exceed 300,000 Euros per submitted project in total.
Information regarding intellectual property / third party infringement used in the context of the submission.
The access to relevant infrastructure to implement the proposed solution is a prerequisite of a collaboration with Boehringer Ingelheim.
Ability to reach tangible results within a timeframe of approximately two years to reach the next decision point.
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.s.
We are currently seeking answers for the following scientific question: Using suitable models, how would you propose to validate the role of TLR5 in cancer immune evasion associated with chronic inflammation?
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 based on mutually agreed funding terms.
We can only accept research proposals if they arrive no later than March 17, 2026, 11:59 pm PST.
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