Melanoma stem cell vaccine induces effective tumor immunity against melanoma

Melanoma stem cells (MSCs)-based vaccine strategies have been a potent immunotherapeutic approach for melanoma treatment, which aimed at inducing specific anti-tumor immunity and targeting cancer stem-like cells. As the main cancer-fighting immune cells, CD8+T cells play an important role in vaccine-induced antitumor immunity. Here, we developed a novel MSC vaccine that induces CD8+T cells to target melanoma stem cells specifically. The MSC vaccine was prepared for our study in order to determine the effectiveness of antitumor immunity. The proportion and activity of CD8+T cells were examined in the spleen after immunization, in particular, the expression and cytotoxicity of the immune checkpoint of spleen lymphocytes were detected by flow cytometry and ELISA, moreover, tumor size and the number of lung metastasis nodules were observed and the specific killing effect of the vaccine was evaluated in immunized mice. We found that the MSC vaccine could promote DCs maturation, activate CD8+T cells, suppress the expression of CTLA-4, PD-1, and Tim-3, and increase the expression of IFN-γ and GzmB of CD8+T cells. Melanoma growth and metastasis were inhibited by the vaccine's specific targeted killing effect. The vaccines based on melanoma stem cells (MSCs) delay the progression of melanoma by inducing anti-tumor immune responses in CD8+T cells.

[1]  M. Salem,et al.  Targeting CD166+ lung cancer stem cells: Molecular study using murine dendritic cell vaccine. , 2021, Toxicology and applied pharmacology.

[2]  Shao-lin Ma,et al.  Fulminant myocarditis induced by immune checkpoint inhibitor nivolumab: a case report and review of the literature , 2021, Journal of Medical Case Reports.

[3]  Guangfu Li,et al.  The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy. , 2021, Cancer letters.

[4]  Agnieszka Cholka,et al.  Prolonged activation of innate immune pathways by a polyvalent STING agonist , 2021, Nature Biomedical Engineering.

[5]  Xiangli Zhao,et al.  Involvement of CD26 in Differentiation and Functions of Th1 and Th17 Subpopulations of T Lymphocytes , 2021, Journal of immunology research.

[6]  Eui-Hong Byun,et al.  Bombyx batryticatus Protein-Rich Extract Induces Maturation of Dendritic Cells and Th1 Polarization: A Potential Immunological Adjuvant for Cancer Vaccine , 2021, Molecules.

[7]  M. Pokrywczyńska,et al.  CD133 Antigen as a Potential Marker of Melanoma Stem Cells: In Vitro and In Vivo Studies , 2020, Stem cells international.

[8]  Beicheng Sun,et al.  One Single Site Clinical Study: To Evaluate the Safety and Efficacy of Immunotherapy With Autologous Dendritic Cells, Cytokine-Induced Killer Cells in Primary Hepatocellular Carcinoma Patients , 2020, Frontiers in Oncology.

[9]  H. Nikzad,et al.  Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma. , 2020, Vaccine.

[10]  D. Spandidos,et al.  Cutaneous melanoma and the immunotherapy revolution (Review) , 2020, International journal of oncology.

[11]  Eui-Hong Byun,et al.  Annona muricata L.-Derived Polysaccharides as a Potential Adjuvant to a Dendritic Cell-Based Vaccine in a Thymoma-Bearing Model , 2020, Nutrients.

[12]  Wei Li,et al.  Immunotherapy: A Potential Approach to Targeting Cancer Stem Cells. , 2020, Current cancer drug targets.

[13]  N. Arsenijević,et al.  Interleukin-33 pretreatment promotes metastatic growth of murine melanoma by reducing the cytotoxic capacity of CD8+ T cells and enhancing regulatory T cells , 2020, Cancer Immunology, Immunotherapy.

[14]  Ying Zheng,et al.  IL33 activates CD8+T and NK cells through MyD88 pathway to suppress the lung cancer cell growth in mice , 2020, Biotechnology Letters.

[15]  A. Onitilo,et al.  Principles of Immunotherapy in Melanoma. , 2020, The Surgical clinics of North America.

[16]  Z. Tian,et al.  Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development , 2019, International journal of cancer.

[17]  M. Stockler,et al.  Preferences for Immunotherapy in Melanoma: A Systematic Review , 2019, Annals of Surgical Oncology.

[18]  Mark E. Davis,et al.  Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers , 2019, Journal of Biomedical Science.

[19]  Jiménez Martínez Yaiza,et al.  Melanoma cancer stem-like cells: Optimization method for culture, enrichment and maintenance. , 2019, Tissue & cell.

[20]  F. Salazar-Onfray,et al.  Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions. , 2019, Immunobiology.

[21]  S. Sleijfer,et al.  CD45RA+CCR7− CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in peripheral blood of NSCLC patients responding to nivolumab , 2019, Journal of Immunotherapy for Cancer.

[22]  S. Yoo,et al.  Recent Advances in Cancer Stem Cell-Targeted Immunotherapy , 2019, Cancers.

[23]  Guangbo Zhang,et al.  IL-33 Released in the Liver Inhibits Tumor Growth via Promotion of CD4+ and CD8+ T Cell Responses in Hepatocellular Carcinoma , 2018, The Journal of Immunology.

[24]  G. Marone,et al.  The Pleiotropic Immunomodulatory Functions of IL-33 and Its Implications in Tumor Immunity , 2018, Front. Immunol..

[25]  Siqing Wang,et al.  IL-33 drives the antitumor effects of dendritic cells via the induction of Tc9 cells , 2018, Cellular & Molecular Immunology.

[26]  D. Tang,et al.  Cancer stem cells: Regulation programs, immunological properties and immunotherapy. , 2018, Seminars in cancer biology.

[27]  Yisheng Gao,et al.  CXCL9 promotes prostate cancer progression through inhibition of cytokines from T cells , 2018, Molecular medicine reports.

[28]  Gang Wang,et al.  Recombinant adenovirus expressing a dendritic cell-targeted melanoma surface antigen for tumor-specific immunotherapy in melanoma mice model. , 2018, Experimental and therapeutic medicine.

[29]  K. Kabashima,et al.  Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations , 2018, Front. Oncol..

[30]  Matthew Collin,et al.  Human dendritic cell subsets: an update , 2018, Immunology.

[31]  Patricia M. Santos,et al.  Dendritic Cell–Based Cancer Vaccines , 2018, The Journal of Immunology.

[32]  J. Dou,et al.  Effective tumor immunity to melanoma mediated by B16F10 cancer stem cell vaccine , 2017, International Immunopharmacology.

[33]  Charles H. Yoon,et al.  An immunogenic personal neoantigen vaccine for patients with melanoma , 2017, Nature.

[34]  T. Kuzel,et al.  Exogenous IL-33 Restores Dendritic Cell Activation and Maturation in Established Cancer , 2017, The Journal of Immunology.

[35]  Siqing Wang,et al.  Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells , 2016, Nature Communications.

[36]  A. Banerjee,et al.  Effector, Memory, and Dysfunctional CD8+ T Cell Fates in the Antitumor Immune Response , 2016, Journal of immunology research.

[37]  J. Dou,et al.  Reinforcing B16F10/GPI-IL-21 vaccine efficacy against melanoma by injecting mice with shZEB1 plasmid or miR200c agomir. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[38]  Marzieh Ebrahimi,et al.  Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses. , 2016, Cancer letters.

[39]  N. Gellrich,et al.  Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo. , 2016, Microvascular research.

[40]  A. Chang,et al.  Promise of cancer stem cell vaccine , 2015, Human vaccines & immunotherapeutics.

[41]  E. Wherry,et al.  Molecular and cellular insights into T cell exhaustion , 2015, Nature Reviews Immunology.

[42]  Y. Qi,et al.  Tumoral Expression of IL-33 Inhibits Tumor Growth and Modifies the Tumor Microenvironment through CD8+ T and NK Cells , 2015, The Journal of Immunology.

[43]  J. Banchereau,et al.  Dendritic-cell-based therapeutic cancer vaccines. , 2013, Immunity.

[44]  A. Chang,et al.  Targeting cancer stem cells via dendritic-cell vaccination , 2012, Oncoimmunology.

[45]  F. Papaccio,et al.  Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  B. Ryffel,et al.  IL‐33‐activated dendritic cells are critical for allergic airway inflammation , 2011, European journal of immunology.

[47]  Qingsheng Li,et al.  Regulating functional cell fates in CD8 T cells , 2010, Immunologic research.

[48]  K. Black,et al.  Antigen‐Specific T‐Cell Response from Dendritic Cell Vaccination Using Cancer Stem‐Like Cell‐Associated Antigens , 2009, Stem cells.

[49]  P. Chu,et al.  Characterization of a subpopulation of colon cancer cells with stem cell‐like properties , 2009, International journal of cancer.

[50]  C. Klebanoff,et al.  CD8+ T‐cell memory in tumor immunology and immunotherapy , 2006, Immunological reviews.

[51]  Ira Mellman,et al.  Cell biology of antigen processing in vitro and in vivo. , 2005, Annual review of immunology.

[52]  Steffen Jung,et al.  Runx3 regulates mouse TGF‐β‐mediated dendritic cell function and its absence results in airway inflammation , 2004, The EMBO journal.

[53]  Eli Gilboa,et al.  Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. , 2000, Nature Medicine.

[54]  J. Mayordomo,et al.  Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity , 1996, The Journal of experimental medicine.

[55]  R. Steinman,et al.  Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses , 1993, The Journal of experimental medicine.