Research Project

Sloan-Kettering Inst Can Research, New York NY

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT – RESEARCH PROJECT Outcomes for cancer patients in low- and middle-income countries (LMIC) like Nigeria are poor compared to high-income countries (HIC). Colorectal cancer (CRC) outcomes, for example, are poor for Nigerian patients when compared to similarly staged patients in the U.S. Advances in immuno-oncology research and the successes of immunotherapy seen in HIC have not been mirrored in LMIC highlighting a critical gap in knowledge that limits global applications of cutting-edge cancer care. This gap in knowledge has implications beyond LMICs, as it limits the development of immunotherapy approaches that are effective across ancestrally varied tumor biology—an urgent need given the highly broad ancestry profile of the U.S. population. Through our work to understand the biology that underlies ancestral differences in cancer outcomes, we have found a higher rate of microsatellite instability (MSI-H) in CRC of Nigerian versus U.S. patients. As MSI-H tumors are immunogenic and potentially sensitive to immune checkpoint blockade, there may be a large proportion of Nigerian patients who may benefit from immunotherapy. However, there are few studies focused on tumor immunology and immuno-oncology in Nigerian CRC. Yet these investigations are vital as we consider the broad application of immunotherapy in LMIC, such as Nigeria. The Nigerian Immuno-Oncology Research (NOLA) program will integrate our expertise in immune-oncology and global cancer initiatives to generate preliminary data, resources, and biobanks for larger future studies. Specifically, in this feasibility and planning phase, we will: 1. characterize the tumor immune microenvironment of Nigerian CRC patients and compare to a reference cohort of U.S. patients; 2. create a whole-slide image pathology dataset of Nigerian CRC patients and controls; and 3. build a biobank for future single-cell analyses of the tumor microenvironment of Nigerian CRC. MSK leads the research project through scientific oversight, technical expertise in tumor immunology, and advanced data analysis. It supports immune profiling, bioinformatics, and comparative analysis of Nigerian and U.S. CRC samples. MSK also mentors Nigerian investigators to build local capacity while generating insights relevant to ancestrally diverse cancer populations in the U.S. The results and resources generated will inform future multi-modal investigations of TME biomarkers associated with tumor immunogenicity/outcome, cost-effective patient stratification for immunotherapy, and rational design of future immunotherapy trials to address the disparate outcomes in Nigerian patients with CRC. This project will not only lay the foundation for a sustainable immuno-oncology research platform in Nigeria but also generate critical insights into tumor immunobiology across ancestries—advancing the global applicability of immunotherapy and informing strategies to improve outcomes among historically understudied populations, including ancestral subgroups within the U.S.