The technological advances occurred in the last few years have led to a great increase in the number of tumor associated antigens TAA that are currently available for clinical applications.
In this review we provide a comprehensive list of human tumor antigens as reported in the literature updated at February The list includes all T cell-defined epitopes, while excluding analogs or artificially modified epitopes, as well as virus-encoded and antibodies-recognized antigens. TAAs are listed in alphabetical order along with the epitope sequence and the HLA allele which restricts recognition by T cells. Data on the tissue distribution of each antigen are also provided together with an extensive bibliography that allows a rapid search for any additional information may be needed on each single antigen or epitope.
Overall, the updated list is a database tool for clinicians, scientists and students who have an interest in the field of tumor immunology and immunotherapy. National Center for Biotechnology Information , U. Didn't get the message? Find out why Add to Clipboard. Add to Collections. DNGR-1 CLEC9A is an internalizing receptor with high expression narrowly restricted to cDC1s in mouse and humans, although it shows low expression on other cell types [ 84 , 85 , , ].
Its main function may be the routing of necrotic cell-derived material into nonlysosomal compartments for cross-presentation [ 55 , , ]. Since cDC1s selectively express the chemokine receptor XCR1, targeting of this receptor with a construct of its ligand XCL1 coupled with antigen was also effective in inducing CD4 and CD8 T-cell-mediated responses against viral infection [ ]. A caveat for the formulation of antigens targeted to DC receptors is that the nature of the most immunogenic tumor antigens is usually ignored.
Indeed, the most powerful tumor antigens are the result of unique non-synonymous mutations in their translated genes whose peptide sequences fit the autologous MHC-I and MHC-II alleles acting as antigen-presenting molecules. Such antigens specific to each tumor are named neoantigens. The use of cancer neoantigens for vaccination holds much promise for the delivery of efficacious immunotherapy strategies [ ], particularly when combined with checkpoint inhibitors [ ]. Targeting neoantigens to cross-priming DCs seems to be a reasonable strategy, but preparing individual DC-targeting moieties for each patient is a daunting biotechnical challenge.
This approach, using neoantigens and shared tumor antigens, is currently being tested in clinical trials against melanoma and breast cancer NCT, NCT Alternatively, naked synthetic mRNA encoding cancer neoantigens can be injected inside LNs with ultrasound guidance achieving powerful vaccine effects [ ]. We will briefly discuss the involvement of cross-priming in currently used therapeutic strategies and the potential for improvement of both cytotoxic therapy and immunotherapy upon combination with cross-priming enhancers.
Chemotherapy can improve immunotherapeutic approaches in two main ways: first, by inducing ICD of tumor cells, allowing for antitumor T-cell cross-priming by native DCs; second, by modulating the phenotype of tumor-associated regulatory populations such as regulatory T cells Tregs , TAMs or myeloid-derived suppressor cells. It is now well known that not all chemotherapeutic agents induce ICD [ ]: anthracyclines such as doxorubicin or mitoxantrone [ , ] and cyclophosphamide [ ] are strong inducers of ICD and tumor antigen cross-presentation, while cisplatin is not [ ].
This suggests a more complex interplay of immune cells involved in the response to chemotherapy. The proimmune effects of chemotherapy may need lower doses than the maximally tolerable dose levels used as a standard [ ]. All in all, the line of work pioneered by Guido Kroemer and Laurence Zitvogel puzzled the world of clinical oncology, since in mouse models some forms of chemotherapy act against tumors with an absolute need for cellular immune responses dependent on ICD [ ].
Ionizing radiation is an ICD inducer, and therefore a good candidate for successful combination with immunotherapy [ , , ]. Radiotherapy RT has been shown to potentiate tumor antigen cross-presentation in mouse models [ ]. Several groups explored the intratumoral injection of DCs into irradiated mouse tumor models with positive results [ , ].
Landscape of Tumor Antigens in T Cell Immunotherapy | The Journal of Immunology
These findings are consistent with the requirement for DC-mediated cross-priming in mouse models in which RT induces abscopal effects to concomitant non-irradiated tumors, that can be greatly potentiated with immunomodulatory anti-PD-1, anti-CTLA-4 and anti-CD mAbs [ — ]. It should be kept in mind that TIDCs under the irradiation beam also undergo functional changes [ ]. Curiously, a conversion from pro- to anti-tumor myeloid populations occurs in the TME of tumors irradiated at low doses [ ].
Active combinations of RT and local TLR agonists have been preclinically reported [ ] and clinically tested against follicular lymphoma [ ] and breast cancer [ ]. Accordingly, if anti-CD47 mAb disrupts this inhibitory interaction, more phagocytosis takes place. Not surprisingly, local immunotherapy based on STING agonist cyclic dinucleotides given intratumorally absolutely requires STING expression in Batf3-dependent DCs [ ] and this function is required to enhance the therapeutic results of immune checkpoint blockade in the B16 melanoma mouse model [ ].
Moreover, Batf3-dependent DCs are critical for the antitumor activity of anti-CD agonist immunostimulatory mAbs [ 13 ].
These results suggest that the numbers of such DCs mediating cross-priming and their activation status can be modulated to enhance other immunotherapy interventions. Direct presentation by malignant cells of tumor antigen to T cells is crucial at the effector killing phase, but inefficient to prime and sustain the cytotoxic immune response [ ].
Cytotoxic T lymphocytes need therefore to recognize their cognate antigen on professional antigen-presenting cells.
Tumor-Reactive T-Cells for Adoptive Immunotherapy
Only a few years ago, cross-priming was a black box in terms of our mechanistic knowledge [ ]. The molecular and cellular details on how, where and under which circumstances cross-presentation of tumor antigens efficiently takes place are crucial for understanding immune responses against tumors and will certainly provide multiple opportunities for progress in cancer immunotherapy.
Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. DC subsets specialized in cross-priming.
Intracellular molecular players in cross-presentation. Evidence for cross-presentation and cross-priming in cancer immunology. Immunogenic cell death and cross-priming. Targeting tumor antigen to DCs to favor its cross-presentation. Cross-priming involvement in various cancer therapies. Oxford Academic. Google Scholar.
A Teijeira. F J Cueto. S Garasa. D Sancho. I Melero.
Sancho and I. Melero authors contributed equally as senior authors. Cite Citation. Permissions Icon Permissions. Abstract Dendritic cells DCs are the main professional antigen-presenting cells for induction of T-cell adaptive responses. Figure 1. Open in new tab Download slide. Figure 2. Figure 3.
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. Search ADS. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets.
Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells. Identification of a novel cell type in peripheral lymphoid organs of mice. Morphology, quantitation, tissue distribution. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity.
Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes.
Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo.
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Bone marrow-derived dendritic cells serve as potent adjuvants for peptide-based antitumor vaccines. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Dendritic cell subsets in primary and secondary T cell responses at body surfaces. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting.
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Le Bon. Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients.
A listing of human tumor antigens recognized by T cells: March 2004 update.
Paradigm shift in dendritic cell-based immunotherapy: from in vitro generated monocyte-derived DCs to naturally circulating DC subsets. Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells.
Immunoproteasomes shape the transcriptome and regulate the function of dendritic cells. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Visualization of immediate immune responses to pioneer metastatic cells in the lung.
Dendritic cells take up and present antigens from viable and apoptotic polymorphonuclear leukocytes.
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