R01CA248931

Variation in Tumor-Associated Immune Profiles and Colorectal Cancer Outcomes

Considerable variability in tumor-associated immune responses exists across racial/ethnic populations. These variations may explain part of the observed disparities in response to cancer therapies, particularly immunotherapy, and treatment outcomes.

In colorectal cancer (CRC), the intensity and composition of tumor infiltrating lymphocytes (TIL) are established prognostic and predictive indicators. However, factors contributing to the diversity of TIL responses observed among CRCs remain largely unknown, and the influence of race/ethnicity and genetic ancestry have been underexplored.

In a recent study comparing CRCs from African Americans and non-Hispanic whites, differences in lymphocytic reactions were observed to partially explain the survival disparity between the two groups. No data is available for other racial/ethnic groups. Prior research has also been limited by relying solely on self-reported race/ethnicity, a significant limitation. Studies show that self-report does not fully or accurately reflect the genetic diversity present in admixed minority populations.

We hypothesize that ancestral genetic architecture is important for shaping immune-related determinants of CRC outcomes given the differential efficiency of immune function observed across racial/ethnic groups. Studies in the genetically admixed Latinx population offer notable advantages, including a unique opportunity to simultaneously tease out the contributions of multiple ancestral backgrounds (e.g. African, European, Indigenous American) to variability in immune function.

Here, we will test the hypothesis that genetic ancestry is independently associated with differences in tumor-associated T cell profiles that contribute to CRC outcome disparities (i.e. observed across populations defined by ethnicity and by genetic ancestry) using existing resources from the Hispanic Colorectal Cancer Study, the Puerto Rico Biobank, the Total Cancer Care Protocol, and the Molecular Epidemiology of Colorectal Cancer Study.

We will address three aims:
(1) Quantify CRC-associated T cell profiles in Latinxs from diverse genetic ancestral backgrounds using DNA- and protein-based approaches.
(2) Investigate the independent associations of genetic ancestry, epidemiologic factors, and clinical variables with T cell profiles in the tumor microenvironment of Latinx CRCs.
(3) Compare CRC-associated T cell profiles between Latinx and non-Hispanic white populations.

This study is unique in leveraging the ancestral diversity of Latinos to understand the relationships between race/ethnicity, germline genetics, tumor immunobiology, and cancer disparities. Results will provide new avenues for understanding immunological factors contributing to disproportionate treatment response and mortality in diverse populations of patients with CRC.

Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Cleveland, Ohio 44195 United States

Single Zip Code

Basic Research in Cancer Health Disparities (R01 Clinical Trials Not Allowed) (PAR-18-654)

Amendment Since initial award the total obligations have increased 375% from $736,864 to $3,497,316.