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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
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The Variations' in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis.

Anna Andrzejczak1, Krzysztof Tupikowski2, Anna Tomkiewicz1

  • 1Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland.

International Journal of Molecular Sciences
|February 11, 2023
PubMed
Summary

Genetic variations in TIM-3 and LGALS9 influence clear cell renal cell carcinoma (ccRCC) risk and patient survival. Specific polymorphisms in TIM-3 and LGALS9 were found to decrease ccRCC susceptibility and impact overall survival.

Keywords:
HAVCR2TIM-3clear cell renal cell carcinoma (ccRCC)disease riskgalectin-9 (LGALS9)immunological checkpointoverall survivalsingle-nucleotide gene polymorphism (SNP)

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Area of Science:

  • Immunogenetics
  • Oncology
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer.
  • T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) and its ligand galectin-9 (LGALS9) are key immune checkpoints.
  • Limited research exists on the role of LGALS9 polymorphisms in cancer risk.

Purpose of the Study:

  • To investigate the association between TIM-3 and LGALS9 gene polymorphisms and ccRCC susceptibility.
  • To evaluate the impact of these polymorphisms on patient overall survival (OS).
  • To analyze the relationship between specific SNPs and clinical features in ccRCC patients.

Main Methods:

  • Genotyping of two TIM-3 SNPs (rs1036199, rs10057302) and four LGALS9 SNPs (rs361497, rs3751093, rs4239242, rs4794976) using TaqMan probes, ARMS-PCR, and RFPL-PCR.
  • Analysis of ccRCC susceptibility and overall survival (OS) in relation to identified genotypes.
  • Subgroup analysis to correlate SNPs with clinical characteristics.

Main Results:

  • The rs10057302 A allele in TIM-3 and the rs4794976 T allele in LGALS9 were associated with a two-fold decrease in ccRCC susceptibility.
  • Specific SNPs showed associations with clinical features of ccRCC.
  • The TIM-3 rs1036199 polymorphism significantly influenced patient overall survival.

Conclusions:

  • Genetic variations in TIM-3 and LGALS9 are linked to both susceptibility to ccRCC and patient outcomes.
  • These findings highlight the potential role of immunogenetic factors in ccRCC development and prognosis.
  • Further research into these polymorphisms could inform personalized risk assessment and treatment strategies for ccRCC.