Evidence map›Paper›PMID 34529108›Full record

ArticleCancer immunology, immunotherapy : CII2022

Immune cell profiles in the tumor microenvironment of early-onset, intermediate-onset, and later-onset colorectal cancer.

Tomotaka Ugai, Juha P Väyrynen, Mai Chan Lau, Jennifer Borowsky, Naohiko Akimoto, Sara A Väyrynen, Melissa Zhao, Rong Zhong, Koichiro Haruki, Andressa Dias Costa and 14 more

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 4 pooled it
2.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 4 syntheses or guidelines pooled it, 48 citations in OpenAlex.

  1. Pooled it
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  17. The Young: Early-Onset Colon Cancer.Clinics in colon and rectal surgery · 2025
    Review
  18. Early Onset Colorectal Cancer: Molecular Underpinnings Accelerating Occurrence.Cellular and molecular gastroenterology and hepatology · 2025
    Review
  19. Review
  20. The global epidemic of early-onset cancer: nature, nurture, or both?Annals of oncology : official journal of the European Society for Medical Oncology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 3 countries.

Tomotaka Ugai *Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Juha P VäyrynenProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Mai Chan LauProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Jennifer Borowsky *Conjoint Gastroenterology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Naohiko AkimotoProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Sara A VäyrynenDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Melissa ZhaoProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Rong ZhongProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Koichiro HarukiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Andressa Dias CostaProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Kenji FujiyoshiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Kota ArimaProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Kana WuDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Andrew T ChanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Yin CaoDivision of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA.
Mingyang SongDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Charles S FuchsYale Cancer Center, New Haven, CT, USA.
Molin WangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jochen K LennerzDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jeffrey A MeyerhardtDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Marios Giannakis *Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jonathan A NowakProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
Shuji Ogino *Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA. sogino@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-3909-2323
Brigham and Women's Hospital · USHarvard University · USBroad Institute · USQIMR Berghofer Medical Research Institute · AUWashington University in St. Louis · USYale Cancer Center · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI RIMM, ERIC B · 1991 to 2009
$41.8M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0M
Cancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5M
Precision Prevention Research ProgramR35CA253185 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Andrew T Chan · 2020 to 2026
$6.9M
Spatial Immunopathological Epidemiology of Colorectal Adenoma-Carcinoma SpectrumR01CA248857 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Jonathan Andrew Nowak, Shuji Ogino · 2020 to 2026
$6.6M
Inflammation and Colorectal NeoplasiaR01CA137178 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAN, ANDREW T · 2009 to 2019
$6.5M
Accelerating Transdisciplinary Epidemiology of Colorectal CancerR35CA197735 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2015 to 2021
$6.0M
Dietary And Lifestyle Determinants Of Colon Cancer Recurrence and SurvivalR01CA118553 · NCI · YALE UNIVERSITY · PI FUCHS, CHARLES S · 2007 to 2019
$4.4M
Cancer Research UK 27140NCI NIH HHS K07 CA188126NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA118553NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA169141NCI NIH HHS R01 CA248857NCI NIH HHS R35 CA197735NCI NIH HHS R35 CA253185NCI NIH HHS R37 CA225655NCI NIH HHS R37 CA246175NCI NIH HHS U01 CA167552NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107NIDDK NIH HHS K24 DK098311NIH HHS K07 CA188126NIH HHS K24 DK098311NIH HHS P01 CA55075NIH HHS P01 CA87969NIH HHS P50 CA127003NIH HHS R01 CA118553NIH HHS R01 CA137178NIH HHS R01 CA151993NIH HHS R01 CA169141NIH HHS R01 CA225655NIH HHS R01 CA248857NIH HHS R35 CA197735NIH HHS U01 CA167552NIH HHS UM1 CA167552NIH HHS UM1 CA186107
6 · The paper itself

Abstract

backgroundDespite heightened interest in early-onset colorectal cancer (CRC) diagnosed before age 50, little is known on immune cell profiles of early-onset CRC. It also remains to be studied whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We therefore hypothesized that immune cell infiltrates in CRC tissue might show differential heterogeneity patterns between three age groups (< 50 "early onset," 50-54 "intermediate onset,"  ≥ 55 "later onset").

methodsWe examined 1,518 incident CRC cases with available tissue data, including 35 early-onset and 73 intermediate-onset cases. To identify immune cells in tumor intraepithelial and stromal areas, we developed three multiplexed immunofluorescence assays combined with digital image analyses and machine learning algorithms, with the following markers: (1) CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 for T cells; (2) CD68, CD86, IRF5, MAF, and MRC1 (CD206) for macrophages; and (3) ARG1, CD14, CD15, CD33, and HLA-DR for myeloid cells.

resultsAlthough no comparisons between age groups showed statistically significant differences at the stringent two-sided α level of 0.005, compared to later-onset CRC, early-onset CRC tended to show lower levels of tumor-infiltrating lymphocytes (P = 0.013), intratumoral periglandular reaction (P = 0.025), and peritumoral lymphocytic reaction (P = 0.044). Compared to later-onset CRC, intermediate-onset CRC tended to show lower densities of overall macrophages (P = 0.050), M1-like macrophages (P = 0.062), CD14

conclusionsThis hypothesis-generating study suggests possible differences in histopathologic lymphocytic reaction patterns, macrophages, and regulatory T cells in the tumor microenvironment by age at diagnosis.

Indexed as

Colorectal NeoplasmsTumor MicroenvironmentHLA-DR AntigensHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedHLA-DR AntigensColorectal neoplasmsImmunologyMolecular pathological epidemiologyYoung onset

Identifiers

PMID34529108
PMCPMC8924022
OpenAlexW3199204024

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.