Unique characteristics of the tumor immune microenvironment in young patients with metastatic colorectal cancer Journal Article
| Authors: | Griffith, B. D.; Lazarus, J.; McGue, J.; Krishnan, S.; D’Angelica, M. I.; Shia, J.; Dobrosotskaya, I.; Shi, J.; Edwards, J.; Rao, A.; Frankel, T. L. |
| Article Title: | Unique characteristics of the tumor immune microenvironment in young patients with metastatic colorectal cancer |
| Abstract: | Introduction: Metastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME). Methods: 111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those <50 years or >65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement. Results: There was no difference in infiltration or proportion of immune cells based upon age, but the younger cohort had a higher proportion of programmed death-ligand 1 (PD-L1)+ expressing antigen presenting cells (APCs) and demonstrated decreased intercellular distance and increased cellular engagement between tumor cells (TCs) and cytotoxic T lymphocytes (CTLs), and between TCs and APCs. These trends were independent of microsatellite instability in tumors. Discussion: Age-related differences in PD-L1 expression and cellular engagement in the tumor microenvironment of patients with mCRC, findings which were unrelated to microsatellite status, suggest a more active immune microenvironment in younger patients that may offer an opportunity for therapeutic intervention with immune based therapy. Copyright © 2023 Griffith, Lazarus, McGue, Krishnan, D’Angelica, Shia, Dobrosotskaya, Shi, Edwards, Rao and Frankel. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; aged; middle aged; area under the curve; colorectal cancer; cd3 antigen; cd8 antigen; cd8+ t lymphocyte; phenotype; metabolism; cancer immunotherapy; image analysis; tumor volume; colonic neoplasms; cohort analysis; colorectal neoplasms; immunotherapy; colorectal tumor; colon tumor; microsatellite instability; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; tumor immunity; tissue microarray; analysis of variance; rectal neoplasms; rectum tumor; antigen presenting cell; immunocompetent cell; cd163 antigen; programmed death 1 ligand 1; programmed death 1 receptor; tumor microenvironment; tumor immunology; metastatic colorectal cancer; diagnostic test accuracy study; metastasis resection; tumor escape; humans; human; male; female; article; b7-h1 antigen; multiplex immunohistochemistry (ihc); spatial relation analysis |
| Journal Title: | Frontiers in Immunology |
| Volume: | 14 |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2023-01-01 |
| Start Page: | 1289402 |
| Language: | English |
| DOI: | 10.3389/fimmu.2023.1289402 |
| PUBMED: | 38152402 |
| PROVIDER: | scopus |
| PMCID: | PMC10751347 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
