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, Kenji Fujiyoshi, Kota Arima, Kana Wu, Andrew T. Chan, Yin Cao, Mingyang Song, Charles S. Fuchs, Molin Wang, Jochen K. Lennerz, Kimmie NgJeffrey A. Meyerhardt, Marios Giannakis, Jonathan A. Nowak, Shuji Ogino

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Despite 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”). Methods: We 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. Results: Although 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+HLA-DR+ cells (P = 0.015), and CD3+CD4+FOXP3+ cells (P = 0.039). Conclusions: This hypothesis-generating study suggests possible differences in histopathologic lymphocytic reaction patterns, macrophages, and regulatory T cells in the tumor microenvironment by age at diagnosis.

Original languageEnglish
Pages (from-to)933-942
Number of pages10
JournalCancer Immunology, Immunotherapy
Issue number4
StatePublished - Apr 2022


  • Colorectal neoplasms
  • Immunology
  • Molecular pathological epidemiology
  • Young onset


Dive into the research topics of 'Immune cell profiles in the tumor microenvironment of early-onset, intermediate-onset, and later-onset colorectal cancer'. Together they form a unique fingerprint.

Cite this