Vol 6, No 3 (2021)
Review article
Published online: 2021-05-10

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Liquid biopsy in targeting gene polymorphism related to the response within immunocheckpoint inhibitors therapeutic regimen

Katarzyna Boguszewska-Byczkiewicz1, Agnieszka Kołacińska-Wow12
Medical Research Journal 2021;6(3):245-248.


Immunotherapy belongs to the group of targeted therapies; it is based on natural immune mechanisms which axis can be promoted or blocked at appropriate points. Breast cancer is the world’s most common cancer among women and in March 2019 the FDA approved the first immunopharmaceutical Atezolizumab, for the treatment of breast cancer. So far, the only registered marker for classification for checkpoint inhibitor therapy has been the presence of PD-L1 receptor expression in tumour cells. A comprehensive search of the literature to elucidate the correlation between PD-1/PD-L1 single nucleotide polymorphism (SNP) and cancer, especially breast cancer or other diseases susceptibility and PD-1/ PD-L1 expression. Seven susceptibility loci was considered: rs41386349, rs7421861, rs36084323, rs11568821, rs2227981, rs10204525, rs2227982. Three of them may be taken into account as potentially helpful in breast cancer patient treatment tailoring: rs36084323, rs2227981, rs2227982.

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  1. Speicher MR, Pantel K. Tumor signatures in the blood. Nat Biotechnol. 2014; 32(5): 441–443.
  2. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018; 103: 356–387.
  3. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017; 377(25): 2500–2501.
  4. Vikas P, Borcherding N, Zhang W. The clinical promise of immunotherapy in triple-negative breast cancer. Cancer Manag Res. 2018; 10: 6823–6833.
  5. Adams S, Schmid P, Rugo HS, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019; 30(3): 397–404.
  6. Adams S, Loi S, Toppmeyer D, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019; 30(3): 405–411.
  7. FDA approves atezolizumab for PD-L1 positive unresectable locally advanced or metastatic triple-negative breast cancer. Case Medical Research. 2019. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atezolizumab-pd-l1-positive-unresectable-locally-advanced-or-metastatic-triple-negative.
  8. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. The EMBO Journal. 1992; 11(11): 3887–3895.
  9. Sharpe AH, Wherry EJ, Ahmed R, et al. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007; 8(3): 239–245.
  10. Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999; 5(12): 1365–1369.
  11. Ren HT, Li YM, Wang XJ, et al. PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women: A Hospital-Based Observational Study. Medicine (Baltimore). 2016; 95(21): e3760.
  12. Hua Z, Li D, Xiang G, et al. PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China. Breast Cancer Res Treat. 2011; 129(1): 195–201.
  13. Teng F, Meng X, Kong Li, et al. Progress and challenges of predictive biomarkers of anti PD-1/PD-L1 immunotherapy: A systematic review. Cancer Lett. 2018; 414: 166–173.
  14. Huang C, Ge T, Xia C, et al. Association of rs10204525 genotype GG and rs2227982 CC combination in programmed cell death 1 with hepatitis B virus infection risk. Medicine (Baltimore). 2019; 98(35): e16972.
  15. Mitchell A, Cordell H, Soemedi R, et al. Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune addison’s disease and graves’ disease susceptibility. Molecular Endocrinology. 2009; 23(11): 1935–1935.
  16. Tseng CC, Lin YZ, Lin CH, et al. Genetic and epigenetic alteration of the programmed cell death 1 in rheumatoid arthritis. Eur J Clin Invest. 2019; 49(10): e13094.
  17. Chun JK, Kang DW, Yoo BW, et al. Programmed death-1 (PD-1) gene polymorphisms lodged in the genetic predispositions of Kawasaki Disease. Eur J Pediatr. 2010; 169(2): 181–185.
  18. Kasamatsu T, Awata M, Ishihara R, et al. PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma. Clin Exp Med. 2020; 20(1): 51–62.
  19. Li F, Fan X, Wang X, et al. Genetic association and interaction of PD1 and TIM3 polymorphisms in susceptibility of chronic hepatitis B virus infection and hepatocarcinogenesis. Discov Med. 2019; 27(147): 79–92.
  20. Zang B, Chen C, Zhao JQ. PD-1 gene rs10204525 and rs7421861 polymorphisms are associated with increased risk and clinical features of esophageal cancer in a Chinese Han population. Aging (Albany NY). 2020; 12(4): 3771–3790.
  21. Hua Z, Li D, Xiang G, et al. PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China. Breast Cancer Res Treat. 2011; 129(1): 195–201.
  22. Li Y, Zhang HL, Kang S, et al. The effect of polymorphisms in PD-1 gene on the risk of epithelial ovarian cancer and patients' outcomes. Gynecol Oncol. 2017; 144(1): 140–145.
  23. Ma Y, Liu X, Zhu J, et al. Polymorphisms of co-inhibitory molecules (CTLA-4/PD-1/PD-L1) and the risk of non-small cell lung cancer in a Chinese population. 8(9):16585-91, 2015. Int J Clin Exp Med. 2015; 8(9): 16585–16591.
  24. Hashemi M, Karami S, Sarabandi S, et al. Association between and Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies. Cancers (Basel). 2019; 11(8).
  25. Hayashi Y, Nishiyama T, Nakatochi M, et al. Association of genetic variants of with recurrent pregnancy loss. Reprod Med Biol. 2018; 17(2): 195–202.
  26. Wu Z, Miao M, Qiu Y, et al. Association between polymorphisms in PDCD1 gene and aplastic anemia in Chinese Han population. Leuk Lymphoma. 2013; 54(10): 2251–2254.
  27. Zhang J, Zhao T, Xu C, et al. The association between polymorphisms in the PDCD1 gene and the risk of cancer: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2016; 95(40): e4423.
  28. Abo El-Khair SM, Sameer W, Awadallah N, et al. Programmed cell death 1 gene polymorphism as a possible risk for systemic lupus erythematosus in Egyptian females. Lupus. 2019; 28(12): 1427–1434.
  29. Prokunina L, Castillejo-López C, Oberg F, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002; 32(4): 666–669.
  30. Li XF, Jiang XQ, Zhang JW, et al. Association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk in a Chinese population. Genet Mol Res. 2016; 15(1).
  31. Yin L, Guo H, Zhao L, et al. The programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with non-small cell lung cancer risk in a Chinese Han population. . Int J Clin Exp Med. 2014; 7(12): 5832–5836.
  32. Savabkar S, Azimzadeh P, Chaleshi V, et al. Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer. Gastroenterol Hepatol Bed Bench. 2013; 6(4): 178–182.
  33. Mojtahedi Z, Mohmedi M, Rahimifar S, et al. Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with colon cancer. Gene. 2012; 508(2): 229–232.
  34. Haghshenas MR, Dabbaghmanesh MH, Miri A, et al. Association of PDCD1 gene markers with susceptibility to thyroid cancer. J Endocrinol Invest. 2017; 40(5): 481–486.
  35. Qiu H, Zheng L, Tang W, et al. Programmed death-1 (PD-1) polymorphisms in Chinese patients with esophageal cancer. Clin Biochem. 2014; 47(7-8): 612–617.
  36. Ali MA, Abdelaziz A, Ali M, et al. PADI4 (rs2240340), PDCD1 (rs10204525), and CTLA4 (231775) gene polymorphisms and polyarticular juvenile idiopathic arthritis. Br J Biomed Sci. 2020; 77(3): 123–128.
  37. Li Z, Li Na, Li F, et al. Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma. Medicine (Baltimore). 2016; 95(52): e5749.
  38. Zhang G, Li Z, Han Q, et al. Altered TNF-α and IFN-γ levels associated with PD1 but not TNFA polymorphisms in patients with chronic HBV infection. Infect Genet Evol. 2011; 11(7): 1624–1630.
  39. Ren HT, Li YM, Wang XJ, et al. PD-1 rs2227982 polymorphism is associated with the decreased risk of breast cancer in northwest Chinese women: a hospital-based observational study. Medicine (Baltimore). 2016; 95(21): e3760.
  40. Tan D, Sheng Li, Yi QH. Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer. Cancer Biomark. 2018; 21(2): 287–297.
  41. Chen Si, Li Y, Deng C, et al. The associations between PD-1, CTLA-4 gene polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis and systemic review. Rheumatol Int. 2016; 36(1): 33–44.