Association between tumour-infiltrating lymphocyte-T CD8+ and programmed death-ligand 1 protein with the occurrence of metastasis in colorectal cancer patients: An observational study
Vol 8, Issue 2, 2024
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Abstract
Background: Tumour-infiltrating lymphocytes CD8+ (TILs CD8+) as an anticancer immune response and Programmed Death-Ligand 1 (PD-L1) as an immune checkpoint molecule expression are important in colorectal cancer (CRC) as their expression correlates with the immune status and the progression of cancer. The primary objective of this study is to examine the relationship between TILs CD8+ and PD-L1 expression levels and CRC metastasis to provide insights into the immune microenvironment’s role in CRC progression and metastasis, potentially improving patient outcomes and treatment response. Methods: This study was an observational study involving colorectal cancer patients who were treated at a tertiary hospital in Bandung, West Java, Indonesia. There were 40 patients included in the study. Tumour tissue samples were collected from patients, and immunohistochemical staining was performed to evaluate TILs CD8+ infiltration and PD-L1 expression levels. Clinical data, including metastasis occurrences, were collected from the cancer registry. Results: Analysis of TILs CD8+ and PD-L1 expression levels in CRC patients revealed significant findings regarding metastasis occurrence and cancer staging. There was a notable positive correlation between PD-L1 expression and TILs-CD8+ infiltration in the presence of distant metastasis and advanced cancer stage (p < 0.05). However, no significant association was observed between TILs CD8 and PD-L1 expression levels and lymphatic metastasis. Conclusion: This study highlights the potential prognostic value of TILs CD8+ and PD-L1 expression levels in predicting CRC progression and metastasis. However, the lack of a significant correlation with lymphatic metastasis suggests the need for further investigation into the underlying mechanisms. Understanding the roles of PD-L1 and TILs-CD8+ expression in CRC metastasis may facilitate the development of targeted therapeutic strategies to improve patient outcomes.
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1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68(6): 394–424. doi: 10.3322/caac.21492
2. Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, et al. Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer. Adv Biomed Res. 2018; 7(1): 28. doi: 10.4103/abr.abr_185_16
3. Bai Z, Zhou Y, Ye Z, et al. Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy. Frontiers in Immunology. 2021; 12. doi: 10.3389/fimmu.2021.808964
4. Raskov H, Orhan A, Christensen JP, et al. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. British Journal of Cancer. 2021; 124(2): 359–367. doi: 10.1038/s41416-020-01048-4
5. Sitompul PIM, Saputra H, Maker LPII, et al. Relationship between Stromal Tumor Infiltrating Lymphocytes (TIL) and Programmed Death-Ligand 1 (PD-L1) expression in Human Epidermal Growth Factor Receptor-2 (HER-2) enriched subtype invasive breast carcinoma at Sanglah General Hospital, Bali, Ind (Indonesian). Intisari Sains Medis. 2021; 12(2): 543–550. doi: 10.15562/ism.v12i2.1021
6. Lotfollahzadeh S, Recio-Boiles A, Colon Cancer CBC. Statpearls [Internet]. 2023. Available online: https://www.ncbi.nlm.nih.gov/books/NBK470380/ (accessed on 5 March 2024).
7. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, et al. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. International Journal of Molecular Sciences. 2017; 18(1): 197. doi: 10.3390/ijms18010197
8. Knowlton CA, Mackay MK, Speer TW, et al. Colon Cancer. In: Brady LW, Yaeger TE (editors). Encyclopedia of Radiation Oncology. Springer; 2023. p. 77.
9. Mattiuzzi C, Sanchis-Gomar F, Lippi G. Concise update on colorectal cancer epidemiology. Annals of Translational Medicine. 2019; 7(21): 609–609. doi: 10.21037/atm.2019.07.91
10. Siegel RL, Wagle NS, Cercek A, et al. Colorectal cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73(3): 233–254. doi: 10.3322/caac.21772
11. Lalos A, Tülek A, Tosti N, et al. Prognostic significance of CD8+ T-cells density in stage III colorectal cancer depends on SDF-1 expression. Scientific Reports. 2021; 11(1): 775. doi: 10.1038/s41598-020-80382-2
12. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nature Reviews Immunology. 2017; 18(3): 153-167. doi: 10.1038/nri.2017.108
13. Liu J, Li J, Luo F, et al. The Predictive Value of CD3+/CD8+ Lymphocyte Infiltration and PD-L1 Expression in Colorectal Cancer. Current Oncology. 2023; 30(11): 9647–9659. doi: 10.3390/curroncol30110699
14. Huang CY, Chiang SF, Ke TW, et al. Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II–III colorectal cancer. Scientific Reports. 2018; 8(1): 1–10. doi: 10.1038/s41598-018-33927-5
15. Irawan E, Lukman K, Usman N, et al. Identification of tumor infiltrating lymphocyte CD8 in Indonesian colorectal cancer population: a cross-sectional study. Bali Medical Journal. 2023; 12(2): 1781–1785. doi: 10.15562/BMJ.V12I2.4520
16. Yin C, Okugawa Y, Yamamoto A, et al. Prognostic significance of CD8+ tumor‑infiltrating lymphocytes and CD66b+ tumor‑associated neutrophils in the invasive margins of stages I‑III colorectal cancer. Oncology Letters. 2022; 24(1). doi: 10.3892/ol.2022.13333
17. Shang S, Yang Y, Chen F, et al. TRIB3 reduces CD8 + T cell infiltration and induces immune evasion by repressing the STAT1-CXCL10 axis in colorectal cancer. Science Translational Medicine. 2022; 14(626). doi: 10.1126/scitranslmed.abf0992
18. Kim JH, Park HE, Cho NY, et al. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. British Journal of Cancer. 2016; 115(4): 490–496. doi: 10.1038/bjc.2016.211
19. Lee LH, Cavalcanti MS, Segal NH, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Modern Pathology. 2016; 29(11): 1433–1442. doi: 10.1038/modpathol.2016.139
20. Shan T, Chen S, Wu T, et al. PD-L1 expression in colon cancer and its relationship with clinical prognosis. Int J Clin Exp Pathol. 2019; 12(5): 1764–1769.
21. Wang L, Ren F, Wang Q, et al. Significance of Programmed Death Ligand 1 (PD-L1) Immunohistochemical Expression in Colorectal Cancer. Molecular Diagnosis & Therapy. 2016; 20(2): 175–181. doi: 10.1007/s40291-016-0188-1
22. Xin H, Zhou C, Wang G, et al. Heterogeneity of PD-L1 expression and CD8 lymphocyte infiltration in metastatic colorectal cancer and their prognostic significance. Heliyon. 2023; 9(2): 1. doi: 10.1016/j.heliyon.2023.e13048
23. Rosenbaum MW, Bledsoe JR, Morales-Oyarvide V, et al. PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Modern Pathology. 2016; 29(9): 1104-1112. doi: 10.1038/modpathol.2016.95
24. Masugi Y, Nishihara R, Yang J, et al. Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut. 2017; 66(8): 1463–1473. doi: 10.1136/gutjnl-2016-311421
25. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer. 2012; 12(4): 252–264. doi: 10.1038/nrc3239
26. Sudoyo AW, Kurniawan AN, Kusumo GD, et al. Increased CD8 Tumor Infiltrating Lymphocytes in Colorectal Cancer Microenvironment Supports an Adaptive Immune Resistance Mechanism of PD-L1 Expression. Asian Pacific Journal of Cancer Prevention. 2019; 20(11): 3421–3427. doi: 10.31557/apjcp.2019.20.11.3421
27. Saleh R, Sasidharan Nair V, Toor SM, et al. Differential gene expression of tumor-infiltrating CD8+T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis. Journal for ImmunoTherapy of Cancer. 2020; 8(2): e001294. doi: 10.1136/jitc-2020-001294
28. Alsalman A, Al-Mterin MA, Murshed K, et al. Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients. Cancers (Basel). 2022; 14(13). doi:10.3390/CANCERS14133194/S1
DOI: https://doi.org/10.24294/ti.v8.i2.6221
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