Trends in Immunotherapy

Article

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

Downloads

https://doi.org/10.24294/ti.v8.i2.6221
Reza Azriyantha, M., Lukman, K., Setya Sulthana, B. A. A., Rudiman, R., Suryawathy Hernowo, B., Sribudiani, Y., Nugraha, P., Irawan, E., & Budiman, D. (2014). 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. Trends in Immunotherapy, 8(2). https://doi.org/10.24294/ti.v8.i2.6221
Volume 8 Issue 2 (2024)
Copyright (c) 2014 Muhammad Reza Azriyantha, Kiki Lukman, Bambang Am Am Setya Sulthana, Reno Rudiman, Bethy Suryawathy Hernowo, Yunia Sribudiani, Prapanca Nugraha, Elit Irawan, Deny Budiman
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Muhammad Reza Azriyantha Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Kiki Lukman
    Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Bambang Am Am Setya Sulthana Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Reno Rudiman Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Bethy Suryawathy Hernowo Department of Pathologic Anatomy, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Yunia Sribudiani Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Prapanca Nugraha Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Elit Irawan Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132
  • Deny Budiman Department of Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung West Java 40132

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.

Keywords:

cancer progression immune response immunomodulation prognostic markers therapeutic targets tumour microenvironment

References

  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