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Simple Summary: Patients with relapsed and refractory T-cell malignancies have poor outlook and limited treatment options. Recently, adoptive cell therapy has emerged as a promising therapy for patients with T-cell malignancies. In this review, we examine the current progress on adoptive cell therapy for T-cell malignancies and discuss the potential future directions. T-cell malignancies are often aggressive and associated with poor prognoses. Adoptive cell therapy has recently shown promise as a new line of therapy for patients with hematological malignancies. However, there are currently challenges in applying adoptive cell therapy to T-cell malignancies. Various approaches have been examined in preclinical and clinical studies to overcome these obstacles. This review aims to provide an overview of the recent progress on adoptive cell therapy for T-cell malignancies. The benefits and drawbacks of different types of adoptive cell therapy are discussed. The potential advantages and current applications of innate immune cell-based adoptive cell therapy for T cell malignancies are emphasized. [ABSTRACT FROM AUTHOR]

With recent clinical breakthroughs, immunotherapy has become the fourth pillar of cancer treatment. Particularly, immune cell-based therapies have been envisioned as a promising treatment option with curative potential for leukemia patients. Hence, an increasing number of preclinical and clinical studies focus on various approaches of immune cell-based therapy for treatment of acute leukemia (AL). However, the use of different immune cell lineages and subsets against different types of leukemia and patient disease statuses challenge the interpretation of the clinical applicability and outcome of immune cell-based therapies. This review aims to provide an overview on recent approaches using various immune cell-based therapies against acute B-, T-, and myeloid leukemias. Further, the apparent limitations observed and potential approaches to overcome these limitations are discussed.

Abstract Objectives This study aimed to explore double-negative T (DNT) cell cytotoxicity to pancreatic cancer and the effect of the Fas (CD95, APO-1)/FasL (CD178) signaling pathway on this process. Methods DNT cells from the peripheral blood of healthy volunteers were expanded in vitro. The inhibitory effect of DNT cells on pancreatic cancer cells was investigated using a CCK-8 assay and nude mouse tumor model. A mechanistic study was performed using pathway blocking assays. Results DNT cells were amplified in vitro with >90% purity, and the growth of pancreatic cancer in vitro was significantly inhibited by DNT cells. After coculture with DNT cells, Fas, caspase-8 and cleaved caspase-8 showed increased expression in pancreatic cancer cells. When blocking agent decoy receptor 3 (DcR3) was added, the antitumor effect of DNT cells and the expression of Fas, caspase-8 and cleaved caspase-8 were reduced in pancreatic cancer cells. In the nude mouse tumor model, the tumor volume and weight were lower in the DNT cell group and gemcitabine group than in the blank control group. Additionally, the expression of Fas, caspase-8 and cleaved caspase-8 was higher in the DNT cell group than in the blank control group. Moreover, DNT cells promoted apoptosis in cancer cells and animal model tissues. Conclusion DNT cells inhibited the growth of pancreatic cancer, and the Fas/FasL signaling pathway was involved in this process. [ABSTRACT FROM AUTHOR]

This research aimed to investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class I chain-related molecules A(MICA) in DNT cell killing pancreatic carcinoma. Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice. Then randomly divided mice into blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. 50 days later mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. DNT cell significantly increased over time. The blank group tumor volume and weight were significantly larger than the other groups (p < 0.001, p < 0.001), but there were no significantly difference between DNT group and gemcitabine group (p > 0.05). Gemcitabine and DNT cell tumor inhibition rate were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than DNT group (p = 0.001, p = 0.003). NKG2D mRNA and protein levels in blank group were significantly lower than DNT cells group (p < 0.001, p = 0.001). In conclusion DNT cell can significantly inhibit the growth of pancreatic carcinoma in vivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D. [ABSTRACT FROM AUTHOR]

T-cell malignancies are often aggressive and associated with poor prognoses. Adoptive cell therapy has recently shown promise as a new line of therapy for patients with hematological malignancies. However, there are currently challenges in applying adoptive cell therapy to T-cell malignancies. Various approaches have been examined in preclinical and clinical studies to overcome these obstacles. This review aims to provide an overview of the recent progress on adoptive cell therapy for T-cell malignancies. The benefits and drawbacks of different types of adoptive cell therapy are discussed. The potential advantages and current applications of innate immune cell-based adoptive cell therapy for T cell malignancies are emphasized.

With recent clinical breakthroughs, immunotherapy has become the fourth pillar of cancer treatment. Particularly, immune cell-based therapies have been envisioned as a promising treatment option with curative potential for leukemia patients. Hence, an increasing number of preclinical and clinical studies focus on various approaches of immune cell-based therapy for treatment of acute leukemia (AL). However, the use of different immune cell lineages and subsets against different types of leukemia and patient disease statuses challenge the interpretation of the clinical applicability and outcome of immune cell-based therapies. This review aims to provide an overview on recent approaches using various immune cell-based therapies against acute B-, T-, and myeloid leukemias. Further, the apparent limitations observed and potential approaches to overcome these limitations are discussed. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore double-negative T (DNT) cell cytotoxicity to pancreatic cancer and the effect of the Fas (CD95, APO-1)/FasL (CD178) signaling pathway on this process., Methods: DNT cells from the peripheral blood of healthy volunteers were expanded in vitro. The inhibitory effect of DNT cells on pancreatic cancer cells was investigated using a CCK-8 assay and nude mouse tumor model. A mechanistic study was performed using pathway blocking assays., Results: DNT cells were amplified in vitro with >90% purity, and the growth of pancreatic cancer in vitro was significantly inhibited by DNT cells. After coculture with DNT cells, Fas, caspase-8 and cleaved caspase-8 showed increased expression in pancreatic cancer cells. When blocking agent decoy receptor 3 (DcR3) was added, the antitumor effect of DNT cells and the expression of Fas, caspase-8 and cleaved caspase-8 were reduced in pancreatic cancer cells. In the nude mouse tumor model, the tumor volume and weight were lower in the DNT cell group and gemcitabine group than in the blank control group. Additionally, the expression of Fas, caspase-8 and cleaved caspase-8 was higher in the DNT cell group than in the blank control group. Moreover, DNT cells promoted apoptosis in cancer cells and animal model tissues., Conclusion: DNT cells inhibited the growth of pancreatic cancer, and the Fas/FasL signaling pathway was involved in this process., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class Ⅰ chain-related molecules A(MICA) on DNT cell killing pancreatic carcinoma. Methods: Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice, and then mice were randomly divided mice into 3 groups, blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. After 40 days mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. Results: The blank group tumor volume and weight of blank group were significantly larger than those of gemcitabine group and DNT group (858.7±35.7 mg, 251.1±19.7 mg, 278.5±17.3 mg, P <0.001), but there were no significantly difference between DNT group and gemcitabine group. The tumor inhibition rate of gemcitabine and DNT cell were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than those in DNT group ( P =0.001, P =0.003). NKG2D mRNA and protein levels in blank group were significantly lower than those in DNT cells group ( P <0.001, P =0.001). Conclusion: DNT cell can significantly inhibit the growth of pancreatic carcinoma in vivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D.