PD1/PDL1 expression is associated with increased TIM3 expression and tumor-infiltrating T lymphocytes in fibroblastic tumors

• H. Chen ^[1] ; H. Liu ^[1] ; J. Ai ^[2] ; X. Du ^[3] ; Y. Sun ^[4] ; S. Xiao ^[5]
  1. [1] Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China
  2. [2] Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China
  3. [3] Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China
  4. [4] Department of Neurobiology, College of Life Sciences, Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, 430074, China
  5. [5] Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 3 (Marzo), 2022, págs. 586-596
• Idioma: inglés
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  • Purpose The combined therapy of inhibiting T cell immunoglobulin domain and mucin domain 3 (TIM3) and programmed cell death 1/programmed death-ligand 1 (PD1/PDL1) has shown encouraging therapeutic effects in some solid tumors. However, the expression of PD1/PDL1 and TIM3 in fibroblastic tumors is ill defined, which has limited the application of these immune checkpoint inhibitors in such tumors.

    Methods Immunostaining of 68 tissue microarray cores of fibroblastic tumors, including intermediate dermatofibrosarcoma protuberans and malignant myxofibrosarcoma and adult-type fibrosarcoma, was used to determine the expression of PD1, PDL1 and TIM3, as well as their relationship with the accumulation of tumor-infiltrating T lymphocytes (TILs).

    Results Both PD1 and PDL1 expression was only observed in a small proportion of fibroblastic tumors, whereas TIM3 was expressed in almost all tumors. However, only the positive expression of PDL1 was related to tumors with high grade and staging. A considerable number of TILs, including CD4- and CD8A-positive T cells and a small group of FoxP3-positive T cells, was also observed in most tumors. The density of TIM3 was positively correlated with that of TILs. Furthermore, higher densities of TIM3, CD4, CD8A and FoxP3 were observed in PD1 and PDL1 double-positive fibroblastic tumors.

    Conclusions This study indicates that TILs with high expression of TIM3 may contribute to immunosuppression in the tumor microenvironment of fibroblastic tumors. Patients with fibroblastic tumors with high expression of PD1/PDL1 and TIM3 may therefore benefit from combination therapy with PD1/PDL1 and TIM3 inhibitors.