Thymic epithelial lesions (TEL) are rare thymic diseases that include thymomas (T), thymic carcinomas (TC), and thymic hyperplasia (TH). TELs are associated with autoimmune disorders (AD) and the pathogenetic link between these diseases is still unknown, although it may rely on the active thymopoiesis (TP) observed in these patients (pts). The identification of possible alterations in TEL TP and their impact on peripheral T cells may allow to understand the immune dysregulation that occurs in these pts. In collaboration with the Humanitas Unit of Thoracic Surgery, we enrolled 22 TELs pts, 9 had AD. T cells from pediatric thymuses and PBMCs from healthy adults were used as controls. Flow-cytometric characterization of circulating and infiltrating T cells was performed by applying an 18-color panel designed in our lab. Our results indicated that TH and type AB Ts, showed an active TP that partially recapitulates the normal one. However, type AB Ts displayed aberrancies in this process, characterized by an increased frequency of CD4+ ISP thymocytes, and by an increased ratio of double-positive over single-positive thymocytes. Notably, tissue-associated and circulating CD8+ T cells of TEL pts with AD showed an increased expression of TIM3 that may act as a compensatory mechanism to reduce chronic tissue damage and may be used as a biomarker for TEL pts follow-up. TP was negligible in TCs, which were rather marked by an increased frequency of mature CD4+ T cells that were composed of up to 35% of CD25+CD127low Treg, which were enriched in a specific subset, characterized by TNFR2 expression, endowed with maximal suppressive activity. Moreover, TCs-infiltrating CD4+ and CD8+ T cells showed increased expression of PD1. Together, these data may support the use of anti-PD1 therapy on TC pts. In conclusion, our result may provide important insights into the comprehension of the interactions between TELs and T cells and pave the way for a personalized therapeutic approach to TEL pts.
Characterization of the tumor-associated T cells in patients with thymic epithelial tumors / S. Balin, S. Franzese, S. Terzoli, E. Fontana, E. Voulaz, M. Perrino, L. DI TOMMASO, A. Villa, P. Zucali, S.A.M. DELLA BELLA, D. Mavilio. ((Intervento presentato al convegno Milan Meets Immunology tenutosi a Milan nel 2022.
Characterization of the tumor-associated T cells in patients with thymic epithelial tumors
S. Balin;S. Franzese;M. Perrino;L. DI TOMMASO;S.A.M. DELLA BELLA;D. Mavilio
2022
Abstract
Thymic epithelial lesions (TEL) are rare thymic diseases that include thymomas (T), thymic carcinomas (TC), and thymic hyperplasia (TH). TELs are associated with autoimmune disorders (AD) and the pathogenetic link between these diseases is still unknown, although it may rely on the active thymopoiesis (TP) observed in these patients (pts). The identification of possible alterations in TEL TP and their impact on peripheral T cells may allow to understand the immune dysregulation that occurs in these pts. In collaboration with the Humanitas Unit of Thoracic Surgery, we enrolled 22 TELs pts, 9 had AD. T cells from pediatric thymuses and PBMCs from healthy adults were used as controls. Flow-cytometric characterization of circulating and infiltrating T cells was performed by applying an 18-color panel designed in our lab. Our results indicated that TH and type AB Ts, showed an active TP that partially recapitulates the normal one. However, type AB Ts displayed aberrancies in this process, characterized by an increased frequency of CD4+ ISP thymocytes, and by an increased ratio of double-positive over single-positive thymocytes. Notably, tissue-associated and circulating CD8+ T cells of TEL pts with AD showed an increased expression of TIM3 that may act as a compensatory mechanism to reduce chronic tissue damage and may be used as a biomarker for TEL pts follow-up. TP was negligible in TCs, which were rather marked by an increased frequency of mature CD4+ T cells that were composed of up to 35% of CD25+CD127low Treg, which were enriched in a specific subset, characterized by TNFR2 expression, endowed with maximal suppressive activity. Moreover, TCs-infiltrating CD4+ and CD8+ T cells showed increased expression of PD1. Together, these data may support the use of anti-PD1 therapy on TC pts. In conclusion, our result may provide important insights into the comprehension of the interactions between TELs and T cells and pave the way for a personalized therapeutic approach to TEL pts.
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