Biomaterial Database

CD4+ T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy. 2022

Minglu Xiao, and Luoyingzi Xie, and Guoshuai Cao, and Shun Lei, and Pengcheng Wang, and Zhengping Wei, and Yuan Luo, and Jingyi Fang, and Xingxing Yang, and Qizhao Huang, and Lifan Xu, and Junyi Guo, and Shuqiong Wen, and Zhiming Wang, and Qing Wu, and Jianfang Tang, and Lisha Wang, and Xiangyu Chen, and Cheng Chen, and Yanyan Zhang, and Wei Yao, and Jianqiang Ye, and Ran He, and Jun Huang, and Lilin Ye

Institute of Immunology, Third Military Medical University, Chongqing, China.

Antitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8+ T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from tumor-derived CD8+ T-cell epitopes can drive the functional exhaustion of tumor-specific CD8+ T cells. Tumor-specific type-I helper CD4+ T (TH1) cells play an important role in the population maintenance and cytotoxic function of exhausted tumor-specific CD8+ T cells in the tumor microenvironment. Nonetheless, whether the vaccination strategy targeting MHC-II-restricted CD4+ T-cell epitopes to induce tumor-specific TH1 responses can confer effective antitumor immunity to restrain tumor growth is not well studied. Here, we developed a heterologous prime-boost vaccination strategy to effectively induce tumor-specific TH1 cells and evaluated its antitumor efficacy and its capacity to potentiate PD-1/PD-L1 immunotherapy. Listeria monocytogenes vector and influenza A virus (PR8 strain) vector stably expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein-specific I-Ab-restricted CD4+ T cell epitope (GP61-80) or ovalbumin-specific CD4+ T cell epitope (OVA323-339) were constructed and evaluated their efficacy against mouse models of melanoma and colorectal adenocarcinoma expressing lymphocytic choriomeningitis virus glycoprotein and ovalbumin. The impact of CD4+ T cell epitope-based heterologous prime-boost vaccination was detected by flow-cytometer, single-cell RNA sequencing and single-cell TCR sequencing. CD4+ T cell epitope-based heterologous prime-boost vaccination efficiently suppressed both mouse melanoma and colorectal adenocarcinoma. This vaccination primarily induced tumor-specific TH1 response, which in turn enhanced the expansion, effector function and clonal breadth of tumor-specific CD8+ T cells. Furthermore, this vaccination strategy synergized PD-L1 blockade mediated tumor suppression. Notably, prime-boost vaccination extended the duration of PD-L1 blockade induced antitumor effects by preventing the re-exhaustion of tumor-specific CD8+ T cells. CD4+ T cell epitope-based heterologous prime-boost vaccination elicited potent both tumor-specific TH1 and CTL response, leading to the efficient tumor control. This strategy can also potentiate PD-1/PD-L1 immune checkpoint blockade (ICB) against cancer.

UI	MeSH Term	Description	Entries
D007167	Immunotherapy	Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.	Immunotherapies
D008545	Melanoma	A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D010047	Ovalbumin	An albumin obtained from the white of eggs. It is a member of the serpin superfamily.	Serpin B14
D011948	Receptors, Antigen, T-Cell	Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.	Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D006023	Glycoproteins	Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins.	C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000082082	Immune Checkpoint Inhibitors	Drugs that block negative regulator IMMUNE CHECKPOINT proteins (e.g., PD-1 RECEPTOR and CTLA-4 ANTIGEN) thereby increasing suppressed immune activation in immunotherapies.	CTLA-4 Inhibitor,CTLA-4 Inhibitors,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitor,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitors,Immune Checkpoint Blockade,Immune Checkpoint Blockers,Immune Checkpoint Inhibition,Immune Checkpoint Inhibitor,PD-1 Inhibitor,PD-1 Inhibitors,PD-1-PD-L1 Blockade,PD-L1 Inhibitor,PD-L1 Inhibitors,Programmed Cell Death Protein 1 Inhibitor,Programmed Cell Death Protein 1 Inhibitors,Programmed Death-Ligand 1 Inhibitors,Blockade, PD-1-PD-L1,CTLA 4 Inhibitor,CTLA 4 Inhibitors,Checkpoint Blockade, Immune,Checkpoint Blockers, Immune,Checkpoint Inhibition, Immune,Checkpoint Inhibitor, Immune,Checkpoint Inhibitors, Immune,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitor,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitors,Inhibitor, PD-1,PD 1 Inhibitor,PD 1 Inhibitors,PD 1 PD L1 Blockade,PD L1 Inhibitor,PD L1 Inhibitors,Programmed Death Ligand 1 Inhibitors
D000230	Adenocarcinoma	A malignant epithelial tumor with a glandular organization.	Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014611	Vaccination	Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.	Immunization, Active,Active Immunization,Active Immunizations,Immunizations, Active,Vaccinations