Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma
Open accessAbstract
Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation. To address these questions, we performed a pilot study to evaluate the patterns of PD-L1 and PD-1 immunohistochemical expression on colorectal carcinoma cells and their tumor-infiltrating lymphocytes, respectively. Using tissue microarray, we found that 5% (19/394) of colorectal carcinomas exhibited high tumor PD-L1 expression, and 19% (76/392) had elevated numbers of PD-1-positive tumor-infiltrating lymphocytes. PD-L1 levels correlated with PD-1 levels (P<0.001), and mismatch-repair-deficient tumors had significantly higher rates of high PD-L1 and PD-1 expression when compared with mismatch-repair-proficient tumors (18% vs 2% and 50% vs 13%, respectively; P<0.001 for both). Staining intensity was also stronger for both markers in mismatch-repair-deficient tumors. Furthermore, we observed that among patients with mismatch-repair-deficient colorectal carcinoma, PD-1/PD-L1 expression stratified recurrence-free survival in an inter-dependent manner: an association between high PD-1-positive tumor-infiltrating lymphocytes and improved recurrence-free survival (P=0.041) was maintained only when the tumors had low-level PD-L1 expression (P=0.006); patients whose tumors had both high PD-1-positive tumor-infiltrating lymphocytes and high PD-L1 expression had a significantly worse recurrence-free survival (P<0.001). Thus, our results not only provide a foundation for further assessment of PD-L1 immunohistochemistry as a predictive marker for anti-PD-1 therapy in colorectal carcinoma, they also shed light on the prognostic impact of tumor-infiltrating lymphocytes in different subsets of mismatch-repair-deficient colorectal carcinomas.
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Expression of PD-L1 in metastatic colorectal cancer is not associated with an immunotherapy response.
“Nevertheless, the expression of PD-L1 in mCRC is not associated with an immunotherapy response [110].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [110]
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- Authors
- Lee, L. H., Cavalcanti, M. S., Segal, N. H., Hechtman, J. F., Weiser, M. R., Smith, J. J., Garcia-Aguilar, J., Sadot, E., Ntiamoah, P., Markowitz, A. J., Shike, M., Stadler, Z. K., Vakiani, E., Klimstra, D. S., & Shia, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Shia, Jinru
- ORCID
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 29
- Issue
- 11
- Pages
- 1433-1442
- ISSN
- 0893-3952 (ISSN-L)
- PMC
- PMC5083129
- OpenAlex
- W2496265832
- Cited by
- 186
- References
- 30
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 19 · 2023: 19 · 2022: 18 · 2021: 15 · 2020: 27 · 2019: 26 · 2018: 26 · 2017: 18 · 2016: 2
- FWCI
- 12.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA008748, NIH/NCI Cancer Center Support Grant P30 CA008748)
- National Cancer Institute (Grant P30-CA008748, CA008748, NIH/NCI Cancer Center Support Grant P30 CA008748., Support Grant P30 CA008748, R01CA182551, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- PD-1, PD-L1, colorectal cancer, mismatch repair deficiency, tumor-infiltrating lymphocytes, immune checkpoint blockade, anti-PD-1 therapy, predictive biomarkers, prognostic factors, recurrence-free survival, tumor immune microenvironment
- MeSH terms
- Adenocarcinoma, Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Pilot Projects, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Proportional Hazards Models, Kaplan-Meier Estimate, Young Adult, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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