PMID- 34717150 OWN - NLM STAT- MEDLINE DCOM- 20220303 LR - 20220303 IS - 1618-0631 (Electronic) IS - 0344-0338 (Linking) VI - 228 DP - 2021 Dec TI - Potential role of immune cell genetic variants associated with tumor microenvironment response in laryngeal squamous cell carcinoma (LSCC) in terms of clinicopathological features. PG - 153665 LID - S0344-0338(21)00326-5 [pii] LID - 10.1016/j.prp.2021.153665 [doi] AB - 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 peripheral 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 distribution 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 clinicopathological relationships detected between CD28 and CD27 genotypes suggest that the hereditary immune checkpoint-dependent T cell traffic may be pathophysiologically important. CI - Copyright (c) 2021. Published by Elsevier GmbH. FAU - Horozoglu, Cem AU - Horozoglu C AD - Department of Medical Biochemistry, Faculty of Medicine, Biruni University, Istanbul, Turkey. Electronic address: cem_horozoglu@hotmail.com. FAU - Sonmez, Dilara AU - Sonmez D AD - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. Electronic address: dilarasnmz@hotmail.com. FAU - Demirkol, Seyda AU - Demirkol S AD - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey; Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, Turkey. Electronic address: seyda.erc@gmail.com. FAU - Hakan, Mehmet Tolgahan AU - Hakan MT AD - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. Electronic address: mthakan@istanbul.edu.tr. FAU - Kaleler, Islim AU - Kaleler I AD - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. Electronic address: islim_kaleler@hotmail.com. FAU - Hepokur, Ceylan AU - Hepokur C AD - Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, Turkey. Electronic address: cozsoy@cumhuriyet.edu.tr. FAU - Verim, Aysegul AU - Verim A AD - Department of Otorhinolaryngology/Head and Neck Surgery, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey. Electronic address: aysegulverim@hotmail.com. FAU - Yaylim, Ilhan AU - Yaylim I AD - Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. Electronic address: ilhanyaylim@gmail.com. LA - eng PT - Journal Article DEP - 20211020 PL - Germany TA - Pathol Res Pract JT - Pathology, research and practice JID - 7806109 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (CD28 Antigens) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7) SB - IM MH - Aged MH - B7-H1 Antigen/genetics MH - CD28 Antigens/genetics MH - Female MH - Genotype MH - Head and Neck Neoplasms/genetics/*immunology/*pathology MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Programmed Cell Death 1 Receptor/genetics MH - Squamous Cell Carcinoma of Head and Neck/genetics/*immunology/*pathology MH - Tumor Microenvironment/*immunology MH - Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics OTO - NOTNLM OT - CD27 OT - CD28 OT - LSCC OT - PD-1 OT - PD-L1 EDAT- 2021/10/31 06:00 MHDA- 2022/03/04 06:00 CRDT- 2021/10/30 20:09 PHST- 2021/07/13 00:00 [received] PHST- 2021/10/12 00:00 [revised] PHST- 2021/10/17 00:00 [accepted] PHST- 2021/10/31 06:00 [pubmed] PHST- 2022/03/04 06:00 [medline] PHST- 2021/10/30 20:09 [entrez] AID - S0344-0338(21)00326-5 [pii] AID - 10.1016/j.prp.2021.153665 [doi] PST - ppublish SO - Pathol Res Pract. 2021 Dec;228:153665. doi: 10.1016/j.prp.2021.153665. Epub 2021 Oct 20.