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Issued by

National Cancer Institute (NCI)

Purpose

 The National Cancer Institute (NCI) is seeking input from the scientific community to identify obstacles and opportunities in the application of systems immunology approaches to reveal underlying principles that regulate immune responses to cancer. This Request for Information (RFI) aims to identify current challenges in the application of systems approaches to advance our understanding of immune system dynamics across the continuum of cancer initiation, progression, invasion, and metastasis, and in the context of prevention, treatment, and intervention. For the purpose of this RFI, cancer systems immunology is defined as the integration of clinical and/or experimental immunology data with computational and mathematical methods to build predictive models of tumor-immune ecosystems that can be tested or validated in a disease-relevant context.

Background

Despite the revolutionary clinical success of various cancer immunotherapies, such as immune checkpoint blockade, adoptive cell therapy, and various immuno-modulatory approaches, long-term outcomes have been restricted to a few cancer types and subsets of patients. While the multivariate components governing the immune mechanisms and underlying processes are being slowly elucidated through reductionist approaches, they have recently become subject to a much more comprehensive characterization enabled through the emergence of single-cell multi-omics, spatial molecular profiling, combined with advances in computational models and artificial intelligence (AI) tools. Despite these advancements, deciphering the intricate nature of the molecular and cellular interactions that orchestrate cancer-immune ecosystems across different tissues and timescales, and that regulate anti-tumor immune responses to various interventions remains a critical need in the field.

To date, preclinical and clinical studies have generated tremendous amounts of data enabling characterization of immune responses and the generation of molecular and cellular atlases along with the tools for their analysis. These important advances are paving the path for discovery in the field of cancer immunology. Many of these studies, however, have been largely descriptive and devoid of functional validation. 

Information Requested

 This RFI aims to identify the challenges faced by cancer systems immunologists to not only characterize tumor-immune ecosystems, but also determine their mechanistic and functional significance, thus enabling the rational design of next generation immunoprevention and immunotherapies and their combinations.

NCI seeks information and actionable recommendations (challenges and solutions) that will enable systems immunology approaches across a wide range of important cancer immunology, immunotherapy, and immunoprevention research problems, such as, but not limited to:

• How environmental, genetic, and/or other predisposing factors communicate with and affect the immune system leading to cancer onset and progression.
• The mechanisms of immune surveillance in the context of pre-malignancy, early lesions, and pre-metastatic settings.
• The tumor-immune co-evolutionary dynamics (including preneoplastic and malignant lesions) underlying immune activation and cancer elimination (before, during, and post-therapy).
• The mechanisms leading to ‘cold’ tumor microenvironments.
• How systemic immune responses and/or peripheral lymphoid organs can contribute to tumor development, progression, and/or control (including response to therapy).
• The role of the microbiota on tumor immunity and response to immunoprevention and immunotherapy.
• How crosstalk between the immune system and other biological systems (e.g., immune-neuro axis, immune-endocrine axis, immune-gut axis, etc.) impacts anti-tumor immune responses or treatment-related toxicity.
• How to leverage existing and emerging resources / tools (e.g., databases, computational tools, analytics tools, etc.) to generate biologically interpretable predictions in cancer immunology, immunotherapy, and immunoprevention.
• Whether systems immunology approaches can overcome discrepancies between animal model responses and patient responses.
• The challenges of using multi-scale (e.g., molecular-cellular-tissue-organism) and/or multi-modal data integration (e.g., genomics, imaging, clinical diagnoses, etc.) to provide mechanistic understanding and/or actionable information.
• How to develop or improve immune-based signatures of early-stage or pre-malignant lesions.
• Whether and how systems immunology approaches can be used to develop cancer prevention strategies. 

Responders to this RFI are welcome to identify other open questions in cancer immunology, immunotherapy, and/or immunoprevention that could benefit from a systems immunology research approach.

Note: Do not include any proprietary or confidential information.

 
 

How to Submit a Response

• Responses will be accepted through February 29, 2024. 
• Responses should be limited to one to two page(s) and marked with this RFI identifier "NOT-CA-24003" in the email subject line as well as in the title of the response.
• Responses in electronic formats are preferred and can be E-mailed to [email protected]
  All individual responses will remain confidential. Any identifiers (e.g., names, institutions, e-mail addresses, etc.) will be removed when responses are compiled. Only the processed, anonymized results will be shared internally with the National Institutes of Health (NIH) staff members and any member of scientific working groups convened by the NCI and NIH, as appropriate.

Respondents will receive an automated e-mail confirmation acknowledging receipt of their response but will not receive any individualized feedback. The NIH will use all information submitted in response to this RFI Notice at its discretion and will not provide comments to any respondent's submission. The NIH may use information gathered by this RFI Notice to inform the development of future funding opportunity announcements and/or in any resultant solicitations.

This RFI Notice is for information and planning purpose only and should not be interpreted as a solicitation or as an obligation on the part of the Federal Government, the NIH, NCI. No monetary awards will be made to pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

Inquiries

Please direct all inquiries to:

Monica Zamisch, PhD
National Cancer Institute (NCI)
Telephone: 240-706-4417
Email: [email protected]