Grant Details
Grant Number: |
1R01CA248857-01 Interpret this number |
Primary Investigator: |
Peters, Ulrike |
Organization: |
Fred Hutchinson Cancer Research Center |
Project Title: |
Interdisciplinary Epidemiologic Consortium to Investigate T-Cell Response in Colorectal Cancer |
Fiscal Year: |
2020 |
Abstract
PROJECT SUMMARY / ABSTRACT
The immune system has pivotal influence in the evolution and progression of many tumor types, including
colorectal cancer (CRC). In particular, the presence of a strong T cell response in CRC, indicating activation of
the adaptive immune system, has been associated with better patient outcomes. As such, recently developed
immunotherapeutic approaches often attempt to harness the adaptive immune response. Immune cells are an
integral component of the tumor microenvironment, and dynamically interact with neoplastic cells. However,
our understanding as to the complexity of the T cell response and the factors that drive this response remains
limited. The objective of this proposal is to identify genetic, lifestyle, and tumor factors associated with the T
cell response in CRC, and to characterize the survival implications of that response. Specifically, in Aim 1 we
will examine the relationship of personal characteristics with T cell response in CRC, including the role of (1a)
germline genetic variation within human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor
(KIR) genes, and (1b) lifestyle factors (e.g., aspirin use, smoking, alcohol consumption). In Aim 2 we will focus
on several colorectal tumor characteristics as they relate to T cell response, including (2a) the presence of
Fusobacterium nucleatum and bacterial toxin genes in CRC, and (2b) somatic mutations in key signaling
pathways (e.g., WNT signaling and RAS/RAF). In Aim 3, we will evaluate the associations of different aspects
of T cell response with CRC survival, accounting for known prognostic factors and the relationships identified in
Aims 1-2. To achieve these Aims, we propose to assess the density and spatial distribution of specific T cell
subsets using multiplexed immunofluorescence (mIF) to quantify expression levels and co-expression patterns
of CD3, CD4, CD8, CD45RO, and FOXP3 at the single cell level. This multiplexed assessment will allow us to
examine the epidemiologic and prognostic relevance of numerous metrics of T cell response in CRC. This
research will leverage the resources of the Genetics and Epidemiology of Colorectal Cancer Consortium
(GECCO) and the Colon Cancer Family Registry (CCFR). GECCO-CCFR is a large collaborative effort
between observational studies of CRC. We have completed genome-wide germline genotyping and have
harmonized epidemiologic data regarding a variety of lifestyle factors and personal characteristics for all
participating studies. We are conducting DNA sequencing with a panel of 205 human genes and a small
number of bacterial genes in CRC tumor tissue. Prospective follow-up for survival is ongoing, and we have
harmonized existing survival data. Through this project, we will add information on T cell response in CRC for
>2,500 CRC cases to the GECCO-CCFR resource. This project provides an unprecedented opportunity to
investigate the epidemiology of the T cell response in CRC and the relationship of that response with personal
and tumor characteristics. Insights gained through this novel study could ultimately inform the development
and targeted implementation of emerging immunotherapeutic and immunopreventative strategies.
Publications
The global epidemic of early-onset cancer: nature, nurture, or both?
Authors: Ogino S.
, Ugai T.
.
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology, 2024-09-16 00:00:00.0; , .
EPub date: 2024-09-16 00:00:00.0.
PMID: 39293513
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Risk of colorectal cancer and adenoma after an appendectomy: results from three large prospective cohort studies and meta-analysis.
Authors: Zhang Y.
, Khil J.
, Feng X.
, Ugai T.
, Ogino S.
, Giovannucci E.
.
Source: Cancer Causes & Control : Ccc, 2024-07-27 00:00:00.0; , .
EPub date: 2024-07-27 00:00:00.0.
PMID: 39066935
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Machine learning links T-cell function and spatial localization to neoadjuvant immunotherapy and clinical outcome in pancreatic cancer.
Authors: Blise K.E.
, Sivagnanam S.
, Betts C.B.
, Betre K.
, Kirchberger N.
, Tate B.J.
, Furth E.E.
, Dias Costa A.
, Nowak J.A.
, Wolpin B.M.
, et al.
.
Source: Cancer Immunology Research, 2024-02-21 00:00:00.0; , .
EPub date: 2024-02-21 00:00:00.0.
PMID: 38381401
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Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients.
Authors: Wesselink E.
, Gauderman W.
, Berndt S.I.
, Brenner H.
, Buchanan D.D.
, Campbell P.T.
, Chan A.T.
, Chang-Claude J.
, Cotterchoi M.
, Gunter M.J.
, et al.
.
Source: Bjc Reports, 2024; 2(1), p. 63.
EPub date: 2024-09-02 00:00:00.0.
PMID: 39233917
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Machine learning links T cell function and spatial localization to neoadjuvant immunotherapy and clinical outcome in pancreatic cancer.
Authors: Blise K.E.
, Sivagnanam S.
, Betts C.B.
, Betre K.
, Kirchberger N.
, Tate B.
, Furth E.E.
, Dias Costa A.
, Nowak J.A.
, Wolpin B.M.
, et al.
.
Source: Biorxiv : The Preprint Server For Biology, 2023-10-23 00:00:00.0; , .
EPub date: 2023-10-23 00:00:00.0.
PMID: 37961410
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Elucidating the Risk of Colorectal Cancer for Variants in Hereditary Colorectal Cancer Genes.
Authors: Mahmood K.
, Thomas M.
, Qu C.
, Gecco-Ccfr Consortium
, Hsu L.
, Buchanan D.D.
, Peters U.
.
Source: Gastroenterology, 2023 Oct; 165(4), p. 1070-1076.e3.
EPub date: 2023-07-14 00:00:00.0.
PMID: 37453563
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Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients.
Authors: Tsai P.C.
, Lee T.H.
, Kuo K.C.
, Su F.Y.
, Lee T.M.
, Marostica E.
, Ugai T.
, Zhao M.
, Lau M.C.
, Väyrynen J.P.
, et al.
.
Source: Nature Communications, 2023-04-13 00:00:00.0; 14(1), p. 2102.
EPub date: 2023-04-13 00:00:00.0.
PMID: 37055393
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Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity.
Authors: Williams H.L.
, Dias Costa A.
, Zhang J.
, Raghavan S.
, Winter P.S.
, Kapner K.S.
, Ginebaugh S.P.
, Väyrynen S.A.
, Väyrynen J.P.
, Yuan C.
, et al.
.
Source: Cancer Research, 2023-02-03 00:00:00.0; 83(3), p. 441-455.
PMID: 36459568
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Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.
Authors: Ugai T.
, Akimoto N.
, Haruki K.
, Harrison T.A.
, Cao Y.
, Qu C.
, Chan A.T.
, Campbell P.T.
, Berndt S.I.
, Buchanan D.D.
, et al.
.
Source: Journal Of Gastroenterology, 2023-01-17 00:00:00.0; , .
EPub date: 2023-01-17 00:00:00.0.
PMID: 36648535
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Molecular Characteristics of Early-onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison to Later-onset Cases: Molecular Characteristics and Early-onset Colorectal Tumor Subsites.
Authors: Ugai T.
, Haruki K.
, Harrison T.A.
, Cao Y.
, Qu C.
, Chan A.T.
, Campbell P.T.
, Akimoto N.
, Berndt S.
, Brenner H.
, et al.
.
Source: The American Journal Of Gastroenterology, 2022-12-30 00:00:00.0; , .
EPub date: 2022-12-30 00:00:00.0.
PMID: 36707929
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Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation and immune response.
Authors: Carreras-Torres R.
, Kim A.E.
, Lin Y.
, Díez-Obrero V.
, Bien S.A.
, Qu C.
, Wang J.
, Dimou N.
, Aglago E.K.
, Albanes D.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2022-12-28 00:00:00.0; , .
EPub date: 2022-12-28 00:00:00.0.
PMID: 36576985
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Neoadjuvant Chemotherapy Is Associated with Altered Immune Cell Infiltration and an Anti-Tumorigenic Microenvironment in Resected Pancreatic Cancer.
Authors: Dias Costa A.
, Väyrynen S.A.
, Chawla A.
, Zhang J.
, Väyrynen J.P.
, Lau M.C.
, Williams H.L.
, Yuan C.
, Morales-Oyarvide V.
, Elganainy D.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2022-12-01 00:00:00.0; 28(23), p. 5167-5179.
PMID: 36129461
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T cell-inflamed gene expression profile is associated with favorable disease-specific survival in non-hypermutated microsatellite-stable colorectal cancer patients.
Authors: Yin H.
, Harrison T.A.
, Thomas S.S.
, Sather C.L.
, Koehne A.L.
, Malen R.C.
, Reedy A.M.
, Wurscher M.A.
, Hsu L.
, Phipps A.I.
, et al.
.
Source: Cancer Medicine, 2022-11-07 00:00:00.0; , .
EPub date: 2022-11-07 00:00:00.0.
PMID: 36341526
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Is early-onset cancer an emerging global epidemic? Current evidence and future implications.
Authors: Ugai T.
, Sasamoto N.
, Lee H.Y.
, Ando M.
, Song M.
, Tamimi R.M.
, Kawachi I.
, Campbell P.T.
, Giovannucci E.L.
, Weiderpass E.
, et al.
.
Source: Nature Reviews. Clinical Oncology, 2022-09-06 00:00:00.0; , .
EPub date: 2022-09-06 00:00:00.0.
PMID: 36068272
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Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science.
Authors: Inamura K.
, Hamada T.
, Bullman S.
, Ugai T.
, Yachida S.
, Ogino S.
.
Source: Gut, 2022-07-12 00:00:00.0; , .
EPub date: 2022-07-12 00:00:00.0.
PMID: 35820782
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Utility of Continuous Disease Subtyping Systems for Improved Evaluation of Etiologic Heterogeneity.
Authors: Li R.
, Ugai T.
, Xu L.
, Zucker D.
, Ogino S.
, Wang M.
.
Source: Cancers, 2022-04-02 00:00:00.0; 14(7), .
EPub date: 2022-04-02 00:00:00.0.
PMID: 35406583
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Smoking and Incidence of Colorectal Cancer Subclassified by Tumor-Associated Macrophage Infiltrates.
Authors: Ugai T.
, Väyrynen J.P.
, Haruki K.
, Akimoto N.
, Lau M.C.
, Zhong R.
, Kishikawa J.
, Väyrynen S.A.
, Zhao M.
, Fujiyoshi K.
, et al.
.
Source: Journal Of The National Cancer Institute, 2022-01-11 00:00:00.0; 114(1), p. 68-77.
PMID: 34264325
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Coffee Intake of Colorectal Cancer Patients and Prognosis According to Histopathologic Lymphocytic Reaction and T-Cell Infiltrates.
Authors: Ugai T.
, Haruki K.
, Väyrynen J.P.
, Borowsky J.
, Fujiyoshi K.
, Lau M.C.
, Akimoto N.
, Zhong R.
, Kishikawa J.
, Arima K.
, et al.
.
Source: Mayo Clinic Proceedings, 2022 01; 97(1), p. 124-133.
PMID: 34996545
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Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer.
Authors: Akimoto N.
, Väyrynen J.P.
, Zhao M.
, Ugai T.
, Fujiyoshi K.
, Borowsky J.
, Zhong R.
, Haruki K.
, Arima K.
, Lau M.C.
, et al.
.
Source: Frontiers In Immunology, 2022; 13, p. 840198.
EPub date: 2022-03-22 00:00:00.0.
PMID: 35392092
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Spatial Organization and Prognostic Significance of NK and NKT-like Cells via Multimarker Analysis of the Colorectal Cancer Microenvironment.
Authors: Väyrynen J.P.
, Haruki K.
, Lau M.C.
, Väyrynen S.A.
, Ugai T.
, Akimoto N.
, Zhong R.
, Zhao M.
, Dias Costa A.
, Borowsky J.
, et al.
.
Source: Cancer Immunology Research, 2021-12-22 00:00:00.0; , .
EPub date: 2021-12-22 00:00:00.0.
PMID: 34937729
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Opportunities for Utilization of DNA Repair Inhibitors in Homologous Recombination Repair-Deficient and Proficient Pancreatic Adenocarcinoma.
Authors: Cleary J.M.
, Wolpin B.M.
, Dougan S.K.
, Raghavan S.
, Singh H.
, Huffman B.
, Sethi N.S.
, Nowak J.A.
, Shapiro G.I.
, Aguirre A.J.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2021-12-15 00:00:00.0; 27(24), p. 6622-6637.
EPub date: 2021-07-20 00:00:00.0.
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Molecular and pathology features of colorectal tumors and patient outcomes are associated with Fusobacterium nucleatum and its subspecies animalis.
Authors: Borozan I.
, Zaidi S.H.
, Harrison T.A.
, Phipps A.I.
, Zheng J.
, Lee S.
, Trinh Q.M.
, Steinfelder R.S.
, Adams J.
, Banbury B.L.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2021-11-04 00:00:00.0; , .
EPub date: 2021-11-04 00:00:00.0.
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Immune cell profiles in the tumor microenvironment of early-onset, intermediate-onset, and later-onset colorectal cancer.
Authors: Ugai T.
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, Borowsky J.
, Akimoto N.
, Väyrynen S.A.
, Zhao M.
, Zhong R.
, Haruki K.
, Dias Costa A.
, et al.
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Source: Cancer Immunology, Immunotherapy : Cii, 2021-09-16 00:00:00.0; , .
EPub date: 2021-09-16 00:00:00.0.
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The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men.
Authors: Sikavi D.R.
, Nguyen L.H.
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, Ugai T.
, Ma W.
, Wang D.D.
, Thompson K.N.
, Yan Y.
, Branck T.
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Source: Clinical And Translational Gastroenterology, 2021-08-01 00:00:00.0; 12(8), p. e00338.
EPub date: 2021-08-01 00:00:00.0.
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Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine.
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, Dewey G.
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Source: Expert Review Of Molecular Diagnostics, 2021-07-26 00:00:00.0; , p. 1-18.
EPub date: 2021-07-26 00:00:00.0.
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The sulfur microbial diet is associated with increased risk of early-onset colorectal cancer precursors.
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, Ma W.
, Wu K.
, Song M.
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Source: Gastroenterology, 2021-07-14 00:00:00.0; , .
EPub date: 2021-07-14 00:00:00.0.
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Prognostic significance of myeloid immune cells and their spatial distribution in the colorectal cancer microenvironment.
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, Dias Costa A.
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, Ugai T.
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Source: Journal For Immunotherapy Of Cancer, 2021 Apr; 9(4), .
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Association of Fusobacterium nucleatum with Specific T Cell Subsets in the Colorectal Carcinoma Microenvironment.
Authors: Borowsky J.
, Haruki K.
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, Ugai T.
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Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2021-02-25 00:00:00.0; , .
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Opinion: Standardizing gene product nomenclature-a call to action.
Authors: Fujiyoshi K.
, Bruford E.A.
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, Sims C.L.
, O'Leary T.J.
, Lo A.W.I.
, Chen N.
, Patel N.R.
, Patel K.P.
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Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2021-01-19 00:00:00.0; 118(3), .
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Dietary intake of branched-chain amino acids and survival after colorectal cancer diagnosis.
Authors: Long L.
, Yang W.
, Liu L.
, Tobias D.K.
, Katagiri R.
, Wu K.
, Jin L.
, Zhang F.F.
, Luo X.
, Liu X.
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Source: International Journal Of Cancer, 2020-12-19 00:00:00.0; , .
EPub date: 2020-12-19 00:00:00.0.
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Rising incidence of early-onset colorectal cancer - a call to action.
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, Hamada T.
, Fujiyoshi K.
, Giannakis M.
, Wu K.
, Cao Y.
, Ng K.
, Ogino S.
.
Source: Nature Reviews. Clinical Oncology, 2020-11-20 00:00:00.0; , .
EPub date: 2020-11-20 00:00:00.0.
PMID: 33219329
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The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor-immune-microbiome interaction.
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, Baba H.
, Ogino S.
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Source: Human Genetics, 2020-11-12 00:00:00.0; , .
EPub date: 2020-11-12 00:00:00.0.
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Genetic variants in the regulatory T cell related pathway and colorectal cancer prognosis.
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, Halama N.
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, Phipps A.I.
, Sakoda L.C.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2020-10-02 00:00:00.0; , .
EPub date: 2020-10-02 00:00:00.0.
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Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer.
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, Arima K.
, Haruki K.
, Kishikawa J.
, Akimoto N.
, Ugai T.
, Lau M.C.
, et al.
.
Source: Ebiomedicine, 2020 Jul; 57, p. 102860.
EPub date: 2020-07-08 00:00:00.0.
PMID: 32652320
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