Clinical trials of cellular therapies for the treatment of colorectal cancer: a narrative review

Colorectal cancer (CRC) treatment using common chemotherapy approaches has drawbacks such as side effects, costs, and resistance of cancer cells which affects patients’ prolonged survival, and quality of life. The immune cells have pivotal roles in regulating tumor progression in the tumor microenvironment (TME). The most important CRC cellular immunotherapies include the use of tumor-derived cells such as tumor-infiltrating lymphocytes (TILs) and lymph node lymphocytes (LNLs), peripheral blood mononuclear cells (PBMCs), derived cells, including T cells, natural killer (NK) cells, cytokine-induced killer (CIK) cells, and chimeric antigen receptor (CAR) cells. Although adoptive cell therapy has some advantages, some disadvantages have been reported. TILs cells are strictly directed against tumor-specific antigens; however, they are inefficient due to immune editing. CIK cells have a major histocompatibility complex (MHC)-independent cytotoxic effect and need concurrent high-dose interleukin (IL)-2 administration. In addition, chimeric antigen receptor-T cells (CAR-T cells) are MHC-independent that overcome MHC downregulation by the tumor. They are potent in recognizing any cell surface antigen and are applicable to a broad range of patients and T-cell populations. Here, the researchers present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance by referring to data obtained from CRC clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy intervention, in combination with other treatments like chemotherapy, radiotherapy, and targeted therapy, is promising for cancer therapy

Investigation of the effects of B16F10 derived exosomes in induction of immunosuppressive phenotype in the hematopoietic stem cells

Objective: This study aimed to elucidate the effects of melanoma-derived exosomes on modulating the differentiation of hematopoietic stem cells (HSCs) towards immunosuppressive myeloid-derived suppressor cells (MDSCs). Materials and Methods: Exosomes were isolated via ultracentrifugation from conditioned media of the B16F10 murine melanoma cell line after adaptation to exosome-free culture conditions. HSCs were extracted from the bone marrow of adult C57BL/6 mice through density gradient separation and MACS column isolation of CD133+ and CD34+ populations. HSCs were cultured with or without B16F10 exosomes for 24 hours. Flow cytometry analyzed the expression of canonical MDSC surface markers CD11b, Ly6G, and Ly6C. Levels of the immunosuppressive cytokines interleukin-10 (IL-10) and tumor necrosis factor beta (TGF-β) in HSC culture supernatants were quantified by ELISA. Results: Compared to untreated controls, HSCs treated with B16F10 exosomes displayed significantly increased percentages of CD11b+Ly6G+ granulocytic MDSCs and CD11b+Ly6C+ monocytic MDSCs, with a notable predominance of the Ly6G+ granulocytic subtype. Additionally, exosome-treated HSCs secreted markedly higher levels of the cytokines IL-10 and TGF-β, which are involved in MDSC-mediated immunosuppression. Conclusions: Our findings demonstrate that melanoma-derived exosomes can orchestrate the differentiation of HSCs into MDSCs with an immunosuppressive phenotype, as evidenced by the upregulation of MDSC surface markers and secreted cytokines. This supports a role for tumor-derived exosomes in driving the systemic expansion and accumulation of immunosuppressive MDSCs through the reprogramming of HSC fate. Elucidating the exosome contents and HSC signaling pathways involved could reveal therapeutic strategies to block this pathway and enhance anti-tumor immunity

Cloud Point Extraction and Flame Atomic Absorption Spectrometry Combination for Copper(II) in Environmental and Biological Samples

A cloud point extraction procedure was presented for the preconcentration of copper(II) ion in various samples. After complexation by 4-(phenyl diazenyl) benzene-1,3-diamine (PDBDM) (chrysoidine), copper(II) ions were quantitatively recovered in Triton X-114 after centrifugation. 0.5 ml of methanol acidified with 1.0 mol L-1 HNO3 was added to the surfactant-rich phase prior to its analysis by flame atomic absorption spectrometry (FAAS). The influence of analytical parameters including ligand. Triton X-114 and HNO3 concentrations, bath temperature, heating time, Centrifuge rate and time were optimized. The effect of the matrix ions on the recovery of copper(II) ions was investigated. The detection limit (3S.D.(b)/m, n = 10) of 0.6 ng mL(-1) along with preconcentration factor of 30 and enrichment factor of 41.1 with R.S.D. of 1.0% for Cu was achieved. The proposed procedure was applied to the analysis of various environmental and biological samples. (C) 2008 Elsevier B.V. All rights reserved