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Evaluation of tumor-infiltrating lymphocytes in osteosarcomas of the jaws: a multicenter study.

Pollianna Muniz AlvesJosé Alcides Almeida de ArrudaDiego Antônio Costa ArantesSara Ferreira Santos CostaLucas Lacerda SouzaHélder Antônio Rebelo PontesFelipe Paiva FonsecaRicardo Alves MesquitaCassiano Francisco Weege NonakaElismauro Francisco MendonçaAline Carvalho Batista
Published in: Virchows Archiv : an international journal of pathology (2018)
The aim of the present study was to investigate the profile of tumor-infiltrating lymphocytes (TIL) in osteosarcomas of the jaws (OSJ). A total of 21 OSJ samples were analyzed in a retrospective and cross-sectional multicenter study. Immunohistochemistry was performed to determine the recognition of TIL such as CD4+, CD8+, granzyme B+ (GrB), programmed cell death protein+ (PD-1), and cytotoxic T lymphocyte-associated antigen 4+ (CTLA-4) in intratumoral and peripheral (stromal) regions. Positivity was determined based on the percentage and density of TIL+ per square millimeter [1 = absent (< 25 cells/mm2), 2 = low (25 to 130 cells/mm2), and 3 = high (> 130 cells/mm2)]. The association of TIL density with clinicopathologic data was determined by the Mann-Whitney test (p < 0.05). OSJ were positive for CD8+ cells in 45% (n = 9) of cases, for CD4+ cells in 30% (n = 6) of cases, and for CTLA-4+ in 4.8% (n = 1) of cases, with a score of 2 (low TIL) in all cases. All cases were negative for GrB and PD-1 (score 1). No association was observed between immune infiltrate and clinicopathologic findings. OSJ showed a microenvironment with low TIL, including failure of effectiveness of the antitumor immune response (absence of GrB+ cells), and few cells exhibited immunotherapeutic targets, such as CTLA-4 and PD-1.
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