Potential role of immune cell genetic variants associated with tumor microenvironment response in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features
Date
20 OctoberAuthor
Horozoglu,CemSonmez, Dilara
Demirkol, Seyda
Hakan, Mehmet Tolgahan
Hepokur, Ceylan
Verim, Aysegul
Yaylim, Ilhan
Metadata
Show full item recordAbstract
Immunomodulatory signals regulate the self-tolerance, activation, priming and survival processes of T cells.
Programmed cell death protein 1 (PD1), Programmed death-ligand 1 (PD-L1) inhibitory signals and CD27, CD28
costimulators have been detected for many solid organ cancers in tumor-infiltrating T cells. It was aimed to
investigate the immune cell-based regulatory genetic variants in laryngeal squamous cell carcinoma (LSCC) in
terms of clinicopathological features. Genotyping was performed by PCR-RFLP method for PD-1 rs2227981, PD L1 rs2890658, CD28 rs3116496, CD27 rs2267966 genetic variants from genomic DNAs extracted from periph eral blood samples in One Hundred Thirty-Six individuals (Sixty-one LSCC and seventy-five controls). Analysis of
SNPs was carried out according to multiple inheritance models (co-dominant, dominant, recessive, over dominant and log-additive). There was no difference between LSCC and control groups in genotype/allele dis tribution for PD-1 and PD-L1 (p > 0.05). In the PD-1 overdominant model, the CT genotype was found to be high
(p = 0.036) in those without a family history. The frequency of C allele (AC+CC) in the PD-L1 dominant model
was higher in alcohol users and those with reflux (p = 0.024; p = 0.001 respectively). In the Dominant model for
PD-L1, the AA genotype was lower in moderately and well-differentiated tumors than in poorly differentiated
tumors (p = 0.02). CD27 AT and CD28 CT genotypes were found to be higher in LSCC patients compared to the
control group (p = 0.009; p = 0.01 respectively), while linkage disequilibrium (LD) was detected between CD27
and CD28 (p = 0.02). In the CD28 dominant model, C allele (CT+CC) carriage was found to be high in those with
family history and in those without reflux and perineural invasion (p = 0.01; p = 0.01; p = 0.03 respectively). In
LSCC, PD-L1 rather than PD-1 has a prognostic effect in terms of clinicopathology, and the LD and clinico pathological relationships detected between CD28 and CD27 genotypes suggest that the hereditary immune
checkpoint-dependent T cell traffic may be pathophysiologically important.