Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment

被引:13
作者
Masaoutis, Christos [1 ]
Palamaris, Kostas [1 ]
Kokkali, Stefania [2 ]
Levidou, Georgia [1 ,3 ]
Theocharis, Stamatios [1 ]
机构
[1] Natl & Kapodistrian Univ Athens, Dept Pathol 1, Med Sch, 75 M Asias Str,Bld 10, GR-11527 Athens, Greece
[2] Natl & Kapodistrian Univ Athens, Oncol Unit, Dept Med 2, Med Sch, 114 V Sofias Str, GR-11527 Athens, Greece
[3] Paracelsus Med Univ, Dept Pathol 2, D-90419 Nurnberg, Germany
关键词
TETs; thymoma; thymic carcinoma; tumor microenvironment; thymocytes; B-cells; immune checkpoint inhibitors; PDL-1; autoimmunity; myasthenia gravis; DEATH-LIGAND; 1; SUPPRESSOR-CELLS; DENDRITIC CELLS; B-CELLS; EXPRESSION; MACROPHAGES; CARCINOMA; THYMOMA; CANCER; PD-L1;
D O I
10.3390/ijms23147864
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thymic Epithelial Tumors (TETs) represent a rare tumor family, originating from the epithelial component of the thymus gland. Clinicopathologically, they are segregated into six major subtypes, associated with distinct histological features and clinical outcomes. Their emergence and evolution are accompanied by the generation of a complex tumor microenvironment (TME), dominated by phenotypically and functionally divergent immune cellular subsets, in different maturation states and in analogies that vary significantly among different subtypes. These heterogenous leukocyte populations exert either immune-permissive and tumor-suppressive functions or vice versa, and the dynamic equilibrium established among them either dictates the tumor immune milieu towards an immune-tolerance state or enables the development of a productive spontaneous tumoricidal response. The immunologically "hot" microenvironment, defining a significant proportion of TETs, makes them a promising candidate for the implementation of immune checkpoint inhibitors (ICIs). A number of phase I and II clinical trials have already demonstrated significant, type-specific clinical efficacy of PD-L1 inhibitors, even though substantial limitations in their utilization derive from their immune-mediated adverse effects. Moreover, the completed clinical studies involved relatively restricted patient samples and an expansion in the enrolled cohorts is required, so that more trustworthy conclusions regarding the benefit from ICIs in TETs can be extracted.
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页数:11
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