Analytic and Dynamic Secretory Profile of Patient-Derived Cytokine-lnduced Killer Cells

Mesiano, Giulia; Zini, Roberta; Montagner, Giulia; Bianchi, Nicoletta; Manfredini, Rossella; Chillemi, Antonella; Aglietta, Massimo; Grignani, Giovanni; Lampronti, Ilaria; Fiorino, Erika; Malavasi, Fabio; Sangiolo, Dario; Gambari, Roberto; Ferrari, Davide

doi:10.2119/molmed.2017.00084

Cited by 10 publications

(6 citation statements)

References 65 publications

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“…Patient-derived CIK cells secrete many cytokines, chemokines, and growth factors [19], such as IFN-γ and TNFα in patients with MDR-TB with bilateral pulmonary lesions and lung cavitation [20]. It may be hypothesized, therefore, that these secreted factors underlie why and how patients with MDR-TB receiving CIK cell treatment might exhibit improved clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis

Tang

Chen

et al. 2022

Journal of Immunology Research

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Objective. Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials. Methods. We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy. Results. Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment. Conclusion. Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB.

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Section: Discussionmentioning

confidence: 99%

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis

Tang

Chen

et al. 2022

Journal of Immunology Research

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“…The mRNA expression data of PBMC and CIK cells originate from Mesiano et al ( 2017 ) and were deposited in the Gene Expression Omnibus repository ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97581 ).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, we performed the gene expression profile (GEP) of PBMC (day 1, absence of INF- γ) and CIK cells (day 14) obtained from 3 GIST patients by means of HG-U219 Array Strip (Affymetrix; Santa Clara, CA, USA) (Mesiano et al, 2017 ). Microarray data were analyzed by using the Partek GS 6.6 Software Package and normalized using the robust multiarray average (RMA) procedure (Irizarry et al, 2003 ).…”

Section: Methodsmentioning

confidence: 99%

Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors

et al. 2018

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Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways. Transcriptome analysis showed the mRNA expression of these molecules and their modulation during PBMC to CIK differentiation. When PBMC from normal subjects or cancer bearing patients were differentiated into CIK cells under normoxic conditions, CD38 and CD39 were greatly up-regulated while the number of CD203a, and CD73 positive cells underwent minor changes. Since hypoxic conditions are often found in tumors, we asked whether CD39, CD38, CD203a, and CD73 expressed by CIK cells were modulated by hypoxia. PBMC isolated from cancer patients and differentiated into CIK cells in hypoxic conditions did not show relevant changes in CD38, CD39, CD73, CD203a, and CD26. CIK cells also expressed A1, A2A, and A2B ADO receptors and they only underwent minor changes as a consequence of hypoxia. The present study sheds light on a previously unknown functional aspect of CIK cells, opening the possibility of pharmacologically modulated ADO-generating ectoezymes to improve CIK cells performance.

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“…Absent of MICA antigen expression has been suggested as a potential predictor of the efficacy of future immunotherapies using cytokine-induced killer (CIK) cells, a T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC) that represent a promising immunological approach in cancer (118). It has been shown that CIK cells are able (i) to produce extracellular ADO via canonical (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways (119) and (ii) to modulate these ectonucleotidases during PBMC to CIK differentiation.…”

Section: Mechanisms Of Resistance To Immunotherapy: Mabs and Immunomomentioning

confidence: 99%

CD38 in Adenosinergic Pathways and Metabolic Re-programming in Human Multiple Myeloma Cells: In-tandem Insights From Basic Science to Therapy

Horenstein¹,

Bracci

Morandi

et al. 2019

Front. Immunol.

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Tumor microenvironments are rich in extracellular nucleotides that can be metabolized by ectoenzymes to produce adenosine, a nucleoside involved in controlling immune responses. Multiple myeloma, a plasma cell malignancy developed within a bone marrow niche, exploits adenosinergic pathways to customize the immune homeostasis of the tumor. CD38, a multifunctional protein that acts as both receptor and ectoenzyme, is overexpressed at all stages of myeloma. At neutral and acidic pH, CD38 catalyzes the extracellular conversion of NAD + to regulators of calcium signaling. The initial disassembly of NAD + is also followed by adenosinergic activity, if CD38 is operating in the presence of CD203a and CD73 nucleotidases. cAMP extruded from tumor cells provides another substrate for metabolizing nucleotidases to signaling adenosine. These pathways flank or bypass the canonical adenosinergic pathway subjected to the conversion of ATP by CD39. All of the adenosinergic networks can be hijacked by the tumor, thus controlling the homeostatic reprogramming of the myeloma in the bone marrow. In this context, adenosine assumes the role of a local hormone: cell metabolism is adjusted via low- or high-affinity purinergic receptors expressed by immune and bone cells as well as by tumor cells. The result is immunosuppression, which contributes to the failure of immune surveillance in cancer. A similar metabolic strategy silences immune effectors during the progression of indolent gammopathies to symptomatic overt multiple myeloma disease. Plasma from myeloma aspirates contains elevated levels of adenosine resulting from interactions between myeloma and other cells lining the niche and adenosine concentrations are known to increase as the disease progresses. This is statistically reflected in the International Staging System for multiple myeloma. Along with the ability to deplete CD38 + malignant plasma cell populations which has led to their widespread therapeutic use, anti-CD38 antibodies are involved in the polarization and release of microvesicles characterized by the expression of multiple adenosine-producing molecules. These adenosinergic pathways provide new immune checkpoints for improving immunotherapy protocols by helping to restore the depressed immune response.

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Analytic and Dynamic Secretory Profile of Patient-Derived Cytokine-lnduced Killer Cells

Cited by 10 publications

References 65 publications

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis

Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors

CD38 in Adenosinergic Pathways and Metabolic Re-programming in Human Multiple Myeloma Cells: In-tandem Insights From Basic Science to Therapy

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