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Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, in vitro expansion, and infusion of tumor-infiltrating or circulating tumor-specific T cells. Although effective in a subset of cases, in the first ACT clinical trials several patients experienced disease progression, in some cases after temporary disease control. This evidence prompted researchers to improve ACT products by taking advantage of the continuously evolving gene engineering field and by improving manufacturing protocols, to enable the generation of effective and long-term persisting tumor-specific T cell products. Despite recent advances, several challenges, including prioritization of antigen targets, identification, and optimization of tumor-specific T cell receptors, in the development of tools enabling T cells to counteract the immunosuppressive tumor microenvironment, still need to be faced. This review aims at summarizing the major achievements, hurdles and possible solutions designed to improve the ACT efficacy and safety profile in the context of liquid and solid tumors.

Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, in vitro expansion, and infusion of tumor-infiltrating or circulating tumor-specific T cells. Although effective in a subset of cases, in the first ACT clinical trials several patients experienced disease progression, in some cases after temporary disease control. This evidence prompted researchers to improve ACT products by taking advantage of the continuously evolving gene engineering field and by improving manufacturing protocols, to enable the generation of effective and long-term persisting tumor-specific T cell products. Despite recent advances, several challenges, including prioritization of antigen targets, identification, and optimization of tumor-specific T cell receptors, in the development of tools enabling T cells to counteract the immunosuppressive tumor microenvironment, still need to be faced. This review aims at summarizing the major achievements, hurdles and possible solutions designed to improve the ACT efficacy and safety profile in the context of liquid and solid tumors. [ABSTRACT FROM AUTHOR]

Upon activation, neutrophils release fibers composed of chromatin and neutrophil proteins termed neutrophil extracellular traps (NETs). NETs trap and kill microbes, activate dendritic cells and T cells, and are implicated in autoimmune and vascular diseases. Given the growing interest in the role of neutrophils in cancer immunoediting and the diverse function of NETs, we searched for NETs release by tumor-associated neutrophils (TANs). Using pediatric Ewing sarcoma (ES) as a model, we retrospectively examined histopathological material from diagnostic biopsies of eight patients (mean ± SD age of 11.5 ± 4.7 years). TANs were found in six patients and in two of those we identified NETs. These two patients presented with metastatic disease and despite entering complete remission after intensive chemotherapy had an early relapse. NETs were not identified in the diagnostic biopsies of two patients with localized disease and two with metastatic disease. This study is the first to show that ANs in ES are activated to make NETs, pointing to a possible role of NETs in cancer. [ABSTRACT FROM AUTHOR]