T‐cell recognition of melanoma‐associated antigens

  title={T‐cell recognition of melanoma‐associated antigens},
  author={Chiara Castelli and Licia Rivoltini and Giovanna Andreola and Matteo Giovanni Giovanni Carrabba and Nicolina Renkvist and Giorgio Parmiani},
  journal={Journal of Cellular Physiology},
In this review, we summarize the significant progress that has been made in the identification of melanoma‐associated antigens (MAA) recognized by cytotoxic T‐lymphocytes (CTL). These antigens belong to three main groups: tumor‐associated testis‐specific antigens (e.g., MAGE, BAGE, and GAGE); melanocyte differentiation antigens (e.g., tyrosinase, Melan‐A/MART‐1); and mutated or aberrantly expressed molecules (e.g, CDK4, MUM‐1, β‐catenin). Although strong CTL activity may be induced ex vivo… 

CD8α+ DC are not the sole subset cross‐presenting cell‐associated tumor antigens from a solid tumor

LN resident CD8α+ DC are not the sole DC subset capable of cross‐presenting cell‐associated tumor antigens, and Migratory tumor DC subsets with altered co‐stimulatory receptor expression may contribute to induction and regulation of tumor‐specific responses.

Review Survivin - a universal tumor antigen

A new tumor antigen, survivin, has been identified on the basis of spontaneous CTL responses in cancer patients, and MHC-restricted survivin epitopes may serve as important and widely applicable targets for anti-cancer immunotherapeutic strategies.

Characterization and Immune Targeting of a Novel Tumor Antigen, EphA2

This thesis has defined a novel tumor antigen, EphA2, and demonstrated the possibility that modulation of its expression in tumor cells may result in increased recognition by specific T effector cells that may be germane to the design of improved and efficacious therapies for the treatment of patients with EPhA2+ tumors.

Survivin--a universal tumor antigen.

A new tumor antigen, survivin, has been identified on the basis of spontaneous CTL responses in different cancer patients, and MHC-restricted survivin epitopes may serve as important and widely applicable targets for anti-cancer immunotherapeutic strategies.

Melanoma vaccines: trials and tribulations

Therapeutic vaccines are more likely to enhance, rather than replace, other anti- melanoma immune therapies, and may be synergistic with products that block T-cell immune checkpoint molecules such as ipilimumab and monoclonal antibodies.

Tumor Antigen Cross-Presentation and the Dendritic Cell: Where it All Begins?

The role of DCs in the cross-presentation of tumor antigen in terms of their subset, function, migration, and location is examined with the intention of examining the early processes that contribute to the development of an ineffective anti-tumor immune response.

Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens.

There is a direct correlation between DNA methylation patterns at the Melan-A/MART-1 promoter region, exogenous Melan’s A/Marts1 promoter activity, and Melan/Mart-1 protein expression, which reveals the division of patient-derived melanoma cell lines into two distinct subsets, which are identical for both uveal and cutaneous tumor types.

Paucity of functional T-cell memory to melanoma antigens in healthy donors and melanoma patients.

  • M. DhodapkarJ. Young N. Bhardwaj
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2000
Despite distinct memory responses to influenza antigens, melanoma patients and healthy controls have a paucity of MA-reactive memory T cells, failing to rapidly generate IFN-gamma-secreting lytic effectors in short-term assays, even when stimulated by DCs.

Cancer vaccines from melanoma to ovarian cancer: good immune responses obtained

The testing of an epitope of this antigen that is recognized by both HLA class-I and class-II restricted CD8+ T cells is reported, which induces integrated humoral and T-cell responses in ovarian cancer.

Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cytotoxic T Lymphocytes

The overall significance of this work is that the newly discovered antigens can be incorporated into a therapeutic vaccine for the treatment of ovarian cancer.



Recognition of melanoma-derived antigens by CTL: possible mechanisms involved in down-regulating anti-tumor T-cell reactivity.

It is hypothesized that one of the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo may be related to the existence of natural analogs of this peptide in other human normal proteins.

Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients

It is demonstrated that systemic TAA-specific T-cell responses can develop de novo in cancer patients, but that antigen-specific unresponsiveness may explain why such cells are unable to control tumor growth.

Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells

Vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma and antigen-specific immunity was induced during DC vaccination.

Immunogenicity of the ALLAVGATK (gp10017 – 25) peptide in HLA‐A3.1 melanoma patients

Data indicate that an in vivo priming leading to a systemic immunity against gp100 in HLA‐A3 melanoma patients may occasionally occur and that the immunogenicity of ALLAVGATK peptide in melanomas patients is comparable to that of other HLA•A2‐restricted epitopes derived from gp100/Mel 17 protein.

Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy.

The results demonstrate that a single antigen can be recognized in the context of two different class I HLA alleles, and suggest that recognition of tyrosinase by antigen-specific T-cells may be involved in tumor rejection.

Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen.

The results suggest that the characterization of the T cell response to melanoma in individual patients and definition of the immunologically relevant genetic defects in tumors may be required to select the most effective therapeutic strategies for a given patient.

Cellular immune response against autologous human malignant melanoma: are in vitro studies providing a framework for a more effective immunotherapy?

After the limited but biologically fundamental clinical responses achieved by adoptive immunotherapy with interleukin-2 and lymphokine-activated killers, T cells appear to lend themselves as crucial new effectors in adoptive Immunotherapy of human cancer and, in particular, of melanoma.

Suboptimal activation of melanoma infiltrating lymphocytes (TIL) due to low avidity of TCR/MHC-tumor peptide interactions

It is shown that melanoma cells, unable to trigger IL- 2 secretion, developed this ability when incubated with the appropriate peptide, indicating that the level of antigens expressed on melanoma tumors critically affects TIL activation status and thus, the efficiency of specific immune reactions mediated by these cells.

Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1.

Results demonstrate that MART-1(27-35) peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy.

The first characterization of a molecular route of escape of tumors from immune recognition in a cohort of patients being treated with immunotherapy is presented, suggesting that the loss of beta 2m may be a mechanism whereby tumor cells can acquire immunoresistance.