Effects of Epithelial to Mesenchymal Transition on T Cell Targeting of Melanoma Cells

Woods, Katherine; Pasam, Anupama; Jayachandran, Aparna; Andrews, Miles C.; Cebon, Jonathan

doi:10.3389/fonc.2014.00367

Cited by 33 publications

(36 citation statements)

References 30 publications

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“…MITF ‐low melanomas have been shown to be resistant to multiple targeted treatments (Müller et al , 2014). Studies have also shown that decreased expression of melanocyte differentiation antigens through downregulation of MITF could possibly trigger immune evasion in melanomas (Kono et al , 2006; Woods et al , 2014). Nonetheless, exact role of MITF in the immune exclusion mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma

et al. 2020

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The presence of immune cells in the tumor microenvironment has been associated with response to immunotherapies across several cancer types, including melanoma. Despite its therapeutic relevance, characterization of the melanoma immune microenvironments remains insufficiently explored. To distinguish the immune microenvironment in a cohort of 180 metastatic melanoma clinical specimens, we developed a method using promoter CpG methylation of immune cell type-specific genes extracted from genome-wide methylation arrays. Unsupervised clustering identified three immune methylation clusters with varying levels of immune CpG methylation that are related to patient survival. Matching protein and gene expression data further corroborated the identified epigenetic characterization. Exploration of the possible immune exclusion mechanisms at play revealed likely dependency on MITF protein level and PTEN loss-of-function events for melanomas unresponsive to immunotherapies (immune-low). To understand whether melanoma tumors resemble other solid tumors in terms of immune methylation characteristics, we explored 15 different solid tumor cohorts from TCGA. Low-dimensional projection based on immune cell type-specific methylation revealed grouping of the solid tumors in line with melanoma immune methylation clusters rather than tumor types. Association of survival outcome with immune cell typespecific methylation differed across tumor and cell types. However, in melanomas immune cell type-specific methylation was associated with inferior patient survival. Exploration of the immune methylation patterns in a pan-cancer context suggested that specific immune microenvironments might occur across the cancer spectrum. Together, our findings underscore the existence of diverse immune microenvironments, which may be informative for future immunotherapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma

et al. 2020

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“…During EMT, phenotypic changes occur and expression of certain tumor antigens is downregulated, thus restraining T cells specific recognition and killing (54). The consequence of EMT on immune system is likely to be dependent on the cancer cell origin.…”

Section: Effect Of Autophagy On Antitumor Immune Responsesmentioning

confidence: 99%

Hijacker of the Antitumor Immune Response: Autophagy Is Showing Its Worst Facet

et al. 2016

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Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism. Emerging evidence point to the prominent role of autophagy in disabling the antitumor immune response by multiple overlapping mechanisms leading to tumor escape from immune cell attack mediated by both natural killer cells and cytotoxic T-lymphocytes. Such a role has inspired significant interest in applying anti-autophagy therapies as an entirely new approach to overcome tumor escape from immune surveillance, which constitutes so far a major challenge in developing more effective cancer immunotherapies. In this review, we will summarize recent reports describing how tumor cells, by activating autophagy, manage to hijack the immune system. In particular, we will focus on the emerging role of hypoxia-induced autophagy in shaping the antitumor immune response and in allowing tumor cells to outmaneuver an effective immune response and escape immunosurveillance. In keeping with this, we strongly believe that autophagy represents an attractive future therapeutic target to develop innovative and effective cancer immunotherapeutic approaches.

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“…Spindle shape morphology and gene expression profiling of cancer cells suggested their mesenchymal-like phenotype [107] . Similarly, a decrease in melan A expression in various melanoma cells following TGF-β incubation (and a switch to the mesenchymal phenotype) was linked to their decreased clearance by melan A recognizing CD8+ T cells in vitro [108] . In a syngeneic mouse BC model, wild-type FVB/N mice injected with neu-expressing (mouse version of HER2) tumor cells with epithelial morphology gave rise to neu-negative tumors showing mesenchymal morphology, consistent with induction of the EMT phenotype [92,109] .…”

Section: Emt In Immune Escapementioning

confidence: 99%

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

Markiewicz

Żaczek²

2017

Pathobiology

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The metastatic spread of cancer accounts for the vast majority of cancer-related deaths. It is mediated by tumor cells circulating in blood (called circulating tumor cells, CTCs), which escaped from their established niches. CTCs give a unique opportunity to look into the metastatic cascade and to study the molecular processes supporting the spread of tumor cells throughout the body. As current therapies are not sufficiently effective in treating metastatic disease, it is important to determine cellular and molecular features of cancer cells that “seed” new tumors in distant organs at early stages. In this review we focus on the role of the epithelial-mesenchymal transition program in providing a survival advantage to metastasizing tumor cells, especially CTCs, and put it in the context of clinical findings.

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Effects of Epithelial to Mesenchymal Transition on T Cell Targeting of Melanoma Cells

Cited by 33 publications

References 30 publications

Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma

Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma

Hijacker of the Antitumor Immune Response: Autophagy Is Showing Its Worst Facet

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

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