Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

Abstract

Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy.

Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

“…31 Since then, MAGE antigens have been used as vaccines in human immunotherapy protocols, resulting in regression of melanomas, as well as other tumor-associated antigens (TAAs), including gp100. 32 The second antigen with the capacity to induce both humoral and cellular immune responses is NY-ESO-1 (cancer-testis antigen 1B), which was isolated from an esophageal squamous cell carcinoma. 33 Like the MAGEs, NY-ESO-1 is expressed by a wide range of cancers, including melanoma.…”

“…Owing to its immunogenic epitopes being detected by human CTLs, gp100 has been used extensively in melanoma vaccines. 32 Another T-cell receptor that has been used for development of melanoma vaccines is the MART-1-specific T-cell receptor, which was reported to be specific to an HLA-A2-specific MART-1 peptide epitope. Autologous CD8-positive T cells genetically engineered to express MART-1-specific T-cell receptors have demonstrated their effective role in immunotherapy of melanoma by inducing melanoma regression and long-term cures in animal models as well as in human patients.…”

“…Autologous CD8-positive T cells genetically engineered to express MART-1-specific T-cell receptors have demonstrated their effective role in immunotherapy of melanoma by inducing melanoma regression and long-term cures in animal models as well as in human patients. 32 Tyrosinase, an oxidase involved in melanin production, is specifically expressed in melanocytes and has been shown to be overexpressed in melanomas. It was also reported to be immunogenic, and tyrosinase-specific CD8-positive T cells can induce lysis of melanoma cell lines.…”

“…HLA-DR-specific tyrosinase peptide epitopes, which are known to be identified by CD4-positive T cells, have been used in vaccines against melanoma, alone or in combination with other TAAs. 32 The immunogenic tyrosinase-related proteins 1 and 2 (TRP-1, TRP-2) are frequently overexpressed in melanoma. TRP-1 is of interest in immunotherapy, and the use of selectively mutated TRP-1 CD8-positive T-cell epitopes is reported to effectively interrupt immunologic tolerance and initiate effective anti-melanoma responses.…”

Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling

“…It is correlated with the proliferation, survival, metastasis, and immune escape of tumor cells [17]. One of the primary reasons for tumor escape from immune surveillance is that the antigen-presenting cells cannot effectively present tumor antigens and activate naive T lymphocytes, which is caused by TME, not the loss of immunogenicity [18,19,20,21,22]. The immunosuppressive TME can produce many cytokines, including VEGF, interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-β 1 (TGF-β 1 ), macrophage colony-stimulating factor (M-CSF), nitric-oxide synthase 2 (NOS2), arginase, cyclooxygenase-2 (COX2), indoleamine-2,3-deoxygenase (IDO), prostaglandin E 2 (PGE 2 ), and ganglioside, which solely or cooperatively affect the recruitment, differentiation, maturation, migration, and survival of DCs [17,21,23].…”