Immunosuppression mediated by regulatory CD8+ T cells in lung cancers
NCI - National Cancer Institute
About This Grant
Abstract Lung cancer is a common and deadly malignancy, accounting for the highest number of cancer-related deaths worldwide. It is divided into two main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Despite groundbreaking advancements in cancer treatment using immune checkpoint blockades (e.g., anti-PD-1/CTLA-4 antibodies), the clinical benefits for lung cancer patients are modest, with a significant fraction of patients failing to respond. Thus, there is an urgent need to improve our understanding of immune evasion mechanisms and develop new therapies to enhance immunotherapy for lung cancer patients. We recently identified KIR+CD8+ T cells as a new type of immunosuppressive cells in humans, which are functional and phenotypic equivalent of Ly49+CD8+ T cells in mice. These cells are elevated in the blood and inflamed tissues of patients with autoimmune or infectious diseases, where they contribute to peripheral tolerance by eliminating pathogenic T cells via their cytolytic activity. Since many tumor antigens are derived from self-molecules, we asked whether these cells are also induced in the tumor microenvironment (TME) to suppress anti-tumor immunity. Our preliminary data showed an increased activity in Ly49+CD8+ T cells in KrasG12DLkb1-/- (KL) NSCLC-bearing mice treated with anti-PD-1 plus anti-CTLA-4 therapy, and depleting these cells significantly enhanced anti-tumor T cell responses in this model. Therefore, we hypothesize that regulatory CD8+ T cells contribute to immune suppression and therapy resistance in lung cancers, and targeting these cells could improve immunotherapy efficacy. To test this hypothesis, we will leverage our innovative murine orthotopic lung cancer models and patient specimens to profile regulatory CD8+ T cells across different lung cancer subtypes and in response to immunotherapy. We will elucidate the mechanisms by which regulatory CD8+ T cells mediate immunosuppression in the TME and assess their potential as therapeutic targets to enhance sensitivity to immunotherapy. Our study may unravel a novel role of regulatory CD8+ T cells in regulating anti-tumor immunity and modulating responses to immunotherapy. By uncovering new cellular dynamics and immunosuppressive mechanisms within the TME, our findings could fundamentally reshape our current understanding on immunosuppression in cancer and support regulatory CD8+ T cells as a new therapeutic target to improve sensitivity to immunotherapy in cancer treatment.
Grant Summary
Immunosuppression mediated by regulatory CD8+ T cells in lung cancers is a NCI - National Cancer Institute grant providing up to $409K for university, nonprofit, healthcare org. Applications are due 2028-02-29 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $409K
2028-02-29
- 1Confirm your organization is eligible for Immunosuppression mediated by regulatory CD8+ T cells in lung cancers from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Immunosuppression mediated by regulatory CD8+ T cells in lung cancers: Frequently Asked Questions
Who is eligible for the Immunosuppression mediated by regulatory CD8+ T cells in lung cancers?
Immunosuppression mediated by regulatory CD8+ T cells in lung cancers is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Immunosuppression mediated by regulatory CD8+ T cells in lung cancers provide?
Immunosuppression mediated by regulatory CD8+ T cells in lung cancers provides up to $409K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Immunosuppression mediated by regulatory CD8+ T cells in lung cancers deadline?
Applications for Immunosuppression mediated by regulatory CD8+ T cells in lung cancers are due 2028-02-29 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Immunosuppression mediated by regulatory CD8+ T cells in lung cancers?
To apply for Immunosuppression mediated by regulatory CD8+ T cells in lung cancers, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.