Carla Mosconi1, José Alcides Almeida de Arruda2, Ana Caroline Rodrigues de Farias1, Gabriella Alves Quixabeira Oliveira1, Henrique Moura de Paula3, Felipe Paiva Fonseca2, Ricardo Alves Mesquita4, Tarcília Aparecida Silva2, Elismauro Francisco Mendonça5, Aline Carvalho Batista6. 1. Department of Stomatology (Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, GO, Brazil. 2. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. 3. Department of Pathology, Hospital Araújo Jorge, Goiânia, GO, Brazil. Electronic address: henrique.depaula@capc.com.br. 4. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: ramesquita@ufmg.br. 5. Department of Stomatology (Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, GO, Brazil. Electronic address: elismaur@ufg.br. 6. Department of Stomatology (Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, GO, Brazil. Electronic address: ali.caba@uol.com.br.
Abstract
OBJECTIVES: The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands. MATERIALS AND METHODS: Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion. RESULTS: ACC showed low CD8+, GrB+ TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates. CONCLUSION: Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.
OBJECTIVES: The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands. MATERIALS AND METHODS: Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion. RESULTS: ACC showed low CD8+, GrB+ TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates. CONCLUSION: Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.
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