HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination

Cabrera, Teresa; Lara, Ester; Romero, José María; Maleno, Isabel; Real, Luis Miguel; Ruiz‐Cabello, Francisco; Valero, Pedro; Camacho, Francisco; Garrido, Federico

doi:10.1007/s00262-006-0226-7

Cited by 76 publications

(56 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in accordance with previous studies and extend the data reported by Vermeulen and coworkers [13,45] and Koopman et al [14] , who suggested that LOH in the 6p21.3 region occurs early and is frequently observed in cervical carcinogenesis. Moreover, a higher haplotype loss was observed in advanced stages of cervical cancer, supporting the concept that the 6p21.3 region, which carries HLA genes, is unstable during malignant transformation of cells, contributing to the mechanism of tumor escape and metastatic progression [46] .…”

Section: Discussionsupporting

confidence: 56%

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Rodríguez¹,

Galeano²,

Palacios

et al. 2011

Pathobiology

View full text Add to dashboard Cite

Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.

show abstract

Section: Discussionsupporting

confidence: 56%

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Rodríguez¹,

Galeano²,

Palacios

et al. 2011

Pathobiology

View full text Add to dashboard Cite

show abstract

“…After many years of rather modest success with tumor vaccination for melanoma [65], investigators had become pessimistic about its potential clinical benefit. Melanoma tumors are probably also driven by cancer stem cells (CSCs), and melanoma CSCs have greatly reduced MHC-I levels [66,67]. Therefore, the T-cell response elicited by the vaccinating peptides would be expected to have only minor effects on the melanoma CSCs, and thus would not be expected to have long-lasting therapeutic effects due to a reduction of this compartment.…”

Section: Optimization Of T-cell Activitymentioning

confidence: 99%

Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics

2012

View full text Add to dashboard Cite

Unmodified antibodies (abs) have been successful in the treatment of hematologic malignancies, but less so for the treatment of solid tumors. They trigger anti-tumor effects through their Fc-domains, and one way to improve their efficacy is to optimize their interaction with the effectors through Fc-engineering. Another way to empower abs is the design of bispecific abs and related fusion proteins allowing a narrower choice of effector cells. Here we review frequently chosen classes of effector cells, as well as common trigger molecules. Natural Killer (NK)-and T-cells are the most investigated populations in therapeutical approaches with bispecific agents until now. Catumaxomab, the first bispecific ab to receive drug approval, targets the tumor antigen Epithelial Cell Adhesion Molecule (EpCAM) and recruits T-cells via a binding site for the cell surface protein CD3. The next generation of recombinant ab-derivatives replaces the broadly reactive Fc-domain by a binding domain for a single selected trigger. Blinatumomab is the first clinically successful member of this class, targeting cancer cells via CD19 and engaging T-cells by CD3. Other investigators have developed related recombinant fusion proteins to recruit effectors, such as NK-cells and macrophages. The first such agents currently in preclinical and clinical development will be discussed.

show abstract

“…102,104 Clinically, decreased MHC class I expression is associated with melanoma progression, therapeutic failure, and poor clinical outcome. [105][106][107] Interestingly, although suppression of MHC class I expression by melanoma stem cells may enable evasion from CD8 þ T lymphocytes of the adaptive immune response, low MHC class I expression would be predicted to increase their susceptibility to NK cells of the innate immune system, which are normally inhibited by MHC class I molecules. However, it is conceivable that melanoma stem cells may escape NK cells by altering their expression of additional surface molecules, such as NK cell ligands, which have activating or inhibitory effects on NK cells.…”

Section: How Melanoma Stem Cells May Evade and Modulate Host Immunitymentioning

confidence: 99%

Melanoma stem cells: not rare, but well done

Girouard

Murphy

2011

Laboratory Investigation

View full text Add to dashboard Cite

Since the identification of self-renewing cells in the hematopoietic system, stem cells have transformed the study of medicine. Cancer biologists have identified stem-like cells in multiple malignancies, including those of solid organs. This has led to the development of a stem cell theory of cancer, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorigenesis. This contrasts with the stochastic model of tumor development, which advances that all tumor cells are capable of tumor formation. Within the field of melanoma, the identity and existence of cancer stem cells has been the subject of recent debate. Much of the controversy may be traced to differences in interpretations and definitions related to the cancer stem cell theory, and the use of dissimilar methodologies to study melanoma cells. Accumulating evidence suggests that cancer stem cells may exist in melanoma, although their frequency may vary and they may be capable of phenotypic plasticity. Importantly, these primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but also may confer virulence via immune evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of melanoma stem cells and the pathways that endow them with virulence hold promise for the design of more effective strategies for amelioration and eradication of this most lethal form of skin cancer.

show abstract

HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination

Cited by 76 publications

References 28 publications

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics

Melanoma stem cells: not rare, but well done

Contact Info

Product

Resources

About