The Relationship between Programmed Cell Death Receptor-1 Expression in Colon Tumoral Tissue and Clinical and Pathological Characteristics of Patients with Colon Cancer

Document Type : Original Article(s)

Authors

1 Medical Student, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Associate Professor, Institute for Cancer Research (ICR), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Activatory or inhibitory immune checkpoints regulate the activity of the immune system. Programmed cell death receptor 1 (PD-1 is an inhibitory immune checkpoint that their overexpression reflects the exhaustion of the immune system. However, it is still unclear how it affects the prognosis of colorectal cancer (CRC). This study aimed to investigate the prognostic value of PD-1 in patients with CRC according to tumor location.
Methods: In a cross-sectional study during 2020-2021, a number of 136 patients with history of CRC who underwent surgery at Al-Zahra Hospital in Isfahan between 2013 and 2017 were selected and evaluated retrospectively. Immuno-histochemical staining of tissue samples was performed for PD-1 marker and the expression of this marker was determined in the center and invasive margins of the tumor. Data on survival and date of death of patients were completed through the patient file and confirmed through the civil registry.
Findings: High expression of PD-1 in invasive margin was significantly related to lower T stage (T1/2) in left tumors, low M stage (M0) in right tumors, absence of metastasis in right and left tumors, larger tumor size
(≥ 5 cm) in right-sided tumors. The expression of this marker in any tumor areas was not significantly related to the survival of the patients.
Conclusion: The findings of this study showed that high expression of PD-1 is related to the lower stages of the CRC, but it is not a good indicator for the prognosis of patients with colon cancer.

Keywords

Main Subjects

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
  2. Merlano MC, Granetto C, Fea E, Ricci V, Garrone O. Heterogeneity of colon cancer: from bench to bedside. ESMO Open. 2017; 2(3): e000218.
  3. Molinari C, Marisi G, Passardi A, Matteucci L, De Maio G, Ulivi P. Heterogeneity in colorectal cancer: a challenge for personalized medicine? Int J Mol Sci 2018; 19(12): 3733.
  4. Bindea G, Mlecnik B, Fridman W-H, Pagès F, Galon J. Natural immunity to cancer in humans. Curr Opin Immunol 2010; 22(2): 215-22.
  5. Angell HK, Bruni D, Barrett JC, Herbst R, Galon J.
    The immunoscore: colon cancer and beyond. Clin Cancer Res 2020; 26(2): 332-9.
  6. Thommen DS, Schumacher TN. T Cell Dysfunction in Cancer. Cancer Cell 2018; 33(4): 547-62.
  7. Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, et al. The clinical role of the TME in solid cancer. Br J Cancer 2019; 120(1): 45-53.
  8. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15(8): 486-99.
  9. Qin S, Xu L, Yi M, Yu S, Wu K, Luo S. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol Cancer 2019; 18(1): 155.
  10. Taylor ES, McCall JL, Girardin A, Munro FM, Black MA, Kemp RA. Functional impairment of infiltrating T cells in human colorectal cancer. Oncoimmunology 2016; 5(11): e1234573.
  11. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res 2020; 10(3): 727-42.
  12. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005; 23: 515-48.
  13. Jiang Y, Chen M, Nie H, Yuan Y. PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations. Hum Vaccin Immunother 2019; 15(5): 1111-22.
  14. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-54.
  15. Shen X, Zhao B. Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis. BMJ 2018;362: k3529.
  16. Berntsson J, Eberhard J, Nodin B, Leandersson K, Larsson AH, Jirström K. Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis. Oncoimmunology 2018; 7(8): e1465165.
  17. Pötzsch M, Berg E, Hummel M, Stein U, von Winterfeld M, Jöhrens K, et al. Better prognosis of gastric cancer patients with high levels of tumor infiltrating lymphocytes is counteracted by PD-1 expression. Oncoimmunology 2020; 9(1): 1824632.
  18. Wu Y, Cao D, Qu L, Cao X, Jia Z, Zhao T, et al. PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer. Oncotarget 2017; 8(38): 64066-82.
  19. Li Y, Liang L, Dai W, Cai G, Xu Y, Li X, et al. Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. Mol Cancer 2016; 15(1): 55.
  20. Lee LH, Cavalcanti MS, Segal NH, Hechtman JF, Weiser MR, Smith JJ, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol 2016; 29(11): 1433-42.
  21. Shibutani M, Maeda K, Nagahara H, Fukuoka T, Nakao S, Matsutani S, et al. The Prognostic Significance of the Tumor-infiltrating Programmed Cell Death-1(+) to CD8(+) Lymphocyte Ratio in Patients with Colorectal Cancer. Anticancer Res 2017; 37(8): 4165-72.
  22. Zengin M, Zergeroğlu S, Okcu O, Benek S. PD-1 and PD-L2 expression predict relapse risk and poor survival in patients with stage III colorectal cancer. Cell Oncol (Dordr) 2021; 44(2): 423-32.
  23. Ahtiainen M, Wirta EV, Kuopio T, Seppälä T, Rantala J, Mecklin JP, et al. Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status. Mod Pathol 2019; 32(6): 866-83.
  24. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al. AJCC cancer staging manual. New York, NY: Springer; 2017.
  25. Gruber ES, Oberhuber G, Pils D, Stork T, Sinn K, Gruber S, et al. The determination of immunomodulation and its impact on survival of rectal cancer patients depends on the area comprising a tissue microarray. Cancers (Basel) 2020; 12(3): 563.
  26. Saleh R, Taha RZ, Toor SM, Sasidharan Nair V, Murshed K, Khawar M, et al. Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer. Cancer Immunol Immunother 2020; 69(10): 1989-99.
  27. Lerrer S, Tocheva AS, Bukhari S, Adam K, Mor A. PD-1-stimulated T cell subsets are transcriptionally and functionally distinct. iScience 2021; 24(9): 103020.
  28. Shen Y, Teng Y, Lv Y, Zhao Y, Qiu Y, Chen W, et al. PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer. J Immunother Cancer 2020; 8(2): e000422.
Journal of Isfahan Medical School
Volume 41, Issue 706
2nd Week, April
March and April 2023
Pages 27-34

Files

History

  • Receive Date: 09 November 2022
  • Revise Date: 13 March 2023
  • Accept Date: 14 March 2023

Share

How to cite

Statistics