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Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing ?-Gal epitopes.

ABSTRACT: Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, ?-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with ?-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured in vitro. The results demonstrated that DCs pulsed with ?-gal-expressing tumor lysate can increase the frequency of CD3+CD8+ CTLs and natural killer T cells, increase the level of tumor necrosis factor-? produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC.

SUBMITTER: Xing X

PROVIDER: S-EPMC6546984 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α-Gal epitopes.

Xing Xiaowei X Zou Zhenyu Z He Changzheng C Hu Zilong Z Liang Kai K Liang Wentao W Wang Yufeng Y Du Xiaohui X

Oncology letters 20190520 1

Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains l ...[more]

PMID: 31289564

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Project description:ObjectiveDendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and experienced complete regression of her lung lesion, continuing to be disease free till date. Hence, the objective of our current study is to evaluate the sustenance or augmentation of immune responses when autologous human papillomavirus positive cervical tumor lysate pulsed DC- are combined with cisplatin, using co-culture assays in vitro.MethodsBefore treatment, peripheral blood and punch biopsy samples were collected from 23 cervical cancer patients after obtaining an informed consent. DC functionality was confirmed through phenotypic and functional assays using autologous peripheral blood mononuclear cells as responders. For cisplatin experiments, the drug was added at 150, 200 (clinical dose equivalent), and 400 μM concentrations to DCs alone or DC-T cell co-cultures. Phenotypic assessment and functional characterization of DCs was done using flow cytometry. Cytokine enzyme-linked immunosorbent assay and interferon (IFN)-γ enzyme-linked immune absorbent spot assays were also performed.ResultsThe functionality of TLDCs was not compromised upon cisplatin treatment in vitro even at the highest (400 μM) concentration. Even though cisplatin treatment reduced the secretion of IFN-γ and interleukin (IL)-12p40 in co-cultures stimulated with TLDCs, this effect was not significant (p>0.05). A doubling of IFN-γ secretion following cisplatin treatment was observed in at least one of three independent experiments. Additional experiments showed a reduction in both FOXP3+ regulatory T cells and IL-10 levels.ConclusionOur results provide evidence that cisplatin treatment may be given after autologous TLDC administration to maintain or improve a productive anti-tumor response in vaccinated patients.

Dataset Information

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing ?-Gal epitopes.

Publications

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α-Gal epitopes.

Similar Datasets

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