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

Abstract

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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