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Effects of epithelial to mesenchymal transition on T cell targeting of melanoma cells.

Woods K, Pasam A, Jayachandran A, Andrews MC, Cebon J - Front Oncol (2014)

Bottom Line: In this perspective article, we address the effects of such phenotype switching on T cell targeting of tumor cells.We assess the effect of changes in the expressed tumor antigen repertoire on T-cell mediated tumor recognition and killing.However, we demonstrate that when targeting antigens whose expression is unaltered during EMT, the capacity of T cells to kill melanoma cell lines in vitro is not influenced by their phenotype.

View Article: PubMed Central - PubMed

Affiliation: Cancer Immunobiology Laboratory, Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Olivia Newton John Cancer and Wellness Centre , Melbourne, VIC , Australia ; School of Cancer Medicine, La Trobe University , Melbourne, VIC , Australia.

ABSTRACT
Melanoma cells can switch phenotype in a manner similar to epithelial to mesenchymal transition (EMT). In this perspective article, we address the effects of such phenotype switching on T cell targeting of tumor cells. During the EMT-like switch in phenotype, a concomitant change in expression of multiple tumor antigens occurs. Melanoma cells undergoing EMT escape from killing by T cells specific for antigens whose expression is downregulated by this process. We discuss melanoma antigens whose expression is influenced by EMT. We assess the effect of changes in the expressed tumor antigen repertoire on T-cell mediated tumor recognition and killing. In addition to escape from T cell immunity via changes in antigen expression, mesenchymal-like melanoma cells are generally more resistant to classical chemotherapy and radiotherapy. However, we demonstrate that when targeting antigens whose expression is unaltered during EMT, the capacity of T cells to kill melanoma cell lines in vitro is not influenced by their phenotype. When considering immune therapies such as cancer vaccination, these data suggest escape from T cell killing due to phenotype switching in melanoma could potentially be avoided by careful selection of target antigen.

No MeSH data available.


Related in: MedlinePlus

Tumor antigen expression in melanoma epithelial or mesenchymal-like cell lines. Microarray-based gene expression of a range of melanoma antigens, including several melanoma differentiation antigens and cancer-testis antigens across a panel of 57 early passage melanoma cell lines and 2 controls (normal melanocytes; “melanocyte” and neonatal melanocytes; “neonatal”). Melanoma cell lines were classified as epithelial-like (top bar; red) or mesenchymal-like (top bar; blue) on the basis of dominant E-cadherin or N-cadherin expression, respectively, however, unsupervised clustering of the cell lines was performed without reference to this annotation. Control melanocytes have been labeled in black.
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Figure 1: Tumor antigen expression in melanoma epithelial or mesenchymal-like cell lines. Microarray-based gene expression of a range of melanoma antigens, including several melanoma differentiation antigens and cancer-testis antigens across a panel of 57 early passage melanoma cell lines and 2 controls (normal melanocytes; “melanocyte” and neonatal melanocytes; “neonatal”). Melanoma cell lines were classified as epithelial-like (top bar; red) or mesenchymal-like (top bar; blue) on the basis of dominant E-cadherin or N-cadherin expression, respectively, however, unsupervised clustering of the cell lines was performed without reference to this annotation. Control melanocytes have been labeled in black.

Mentions: We assessed gene expression in our panel of 57 early passage melanoma cell lines (7, 24). Cell lines were classified as E-like or M-like on the basis of E-cadherin or N-cadherin expression, respectively. We have previously reported widespread variation in antigen expression between E- or M-like phenotypes (8). Here, we focus on the difference in expression of a range of immunogenic antigens, including MDA and CTAg, shown in Figure 1. As previously reported by ourselves and others, expression of MDA (e.g., Melan-A and tyrosinase) and MITF was largely lower in M-like, compared to E-like, cells. In contrast, a number of CTAg (e.g., SPANX family members) were upregulated in M-like cells. The expression of some antigens (e.g., MAGED1) was unaffected by the differences in phenotype between our cell lines. These data highlight the immunogenic heterogeneity of melanoma.


Effects of epithelial to mesenchymal transition on T cell targeting of melanoma cells.

Woods K, Pasam A, Jayachandran A, Andrews MC, Cebon J - Front Oncol (2014)

Tumor antigen expression in melanoma epithelial or mesenchymal-like cell lines. Microarray-based gene expression of a range of melanoma antigens, including several melanoma differentiation antigens and cancer-testis antigens across a panel of 57 early passage melanoma cell lines and 2 controls (normal melanocytes; “melanocyte” and neonatal melanocytes; “neonatal”). Melanoma cell lines were classified as epithelial-like (top bar; red) or mesenchymal-like (top bar; blue) on the basis of dominant E-cadherin or N-cadherin expression, respectively, however, unsupervised clustering of the cell lines was performed without reference to this annotation. Control melanocytes have been labeled in black.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269118&req=5

Figure 1: Tumor antigen expression in melanoma epithelial or mesenchymal-like cell lines. Microarray-based gene expression of a range of melanoma antigens, including several melanoma differentiation antigens and cancer-testis antigens across a panel of 57 early passage melanoma cell lines and 2 controls (normal melanocytes; “melanocyte” and neonatal melanocytes; “neonatal”). Melanoma cell lines were classified as epithelial-like (top bar; red) or mesenchymal-like (top bar; blue) on the basis of dominant E-cadherin or N-cadherin expression, respectively, however, unsupervised clustering of the cell lines was performed without reference to this annotation. Control melanocytes have been labeled in black.
Mentions: We assessed gene expression in our panel of 57 early passage melanoma cell lines (7, 24). Cell lines were classified as E-like or M-like on the basis of E-cadherin or N-cadherin expression, respectively. We have previously reported widespread variation in antigen expression between E- or M-like phenotypes (8). Here, we focus on the difference in expression of a range of immunogenic antigens, including MDA and CTAg, shown in Figure 1. As previously reported by ourselves and others, expression of MDA (e.g., Melan-A and tyrosinase) and MITF was largely lower in M-like, compared to E-like, cells. In contrast, a number of CTAg (e.g., SPANX family members) were upregulated in M-like cells. The expression of some antigens (e.g., MAGED1) was unaffected by the differences in phenotype between our cell lines. These data highlight the immunogenic heterogeneity of melanoma.

Bottom Line: In this perspective article, we address the effects of such phenotype switching on T cell targeting of tumor cells.We assess the effect of changes in the expressed tumor antigen repertoire on T-cell mediated tumor recognition and killing.However, we demonstrate that when targeting antigens whose expression is unaltered during EMT, the capacity of T cells to kill melanoma cell lines in vitro is not influenced by their phenotype.

View Article: PubMed Central - PubMed

Affiliation: Cancer Immunobiology Laboratory, Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Olivia Newton John Cancer and Wellness Centre , Melbourne, VIC , Australia ; School of Cancer Medicine, La Trobe University , Melbourne, VIC , Australia.

ABSTRACT
Melanoma cells can switch phenotype in a manner similar to epithelial to mesenchymal transition (EMT). In this perspective article, we address the effects of such phenotype switching on T cell targeting of tumor cells. During the EMT-like switch in phenotype, a concomitant change in expression of multiple tumor antigens occurs. Melanoma cells undergoing EMT escape from killing by T cells specific for antigens whose expression is downregulated by this process. We discuss melanoma antigens whose expression is influenced by EMT. We assess the effect of changes in the expressed tumor antigen repertoire on T-cell mediated tumor recognition and killing. In addition to escape from T cell immunity via changes in antigen expression, mesenchymal-like melanoma cells are generally more resistant to classical chemotherapy and radiotherapy. However, we demonstrate that when targeting antigens whose expression is unaltered during EMT, the capacity of T cells to kill melanoma cell lines in vitro is not influenced by their phenotype. When considering immune therapies such as cancer vaccination, these data suggest escape from T cell killing due to phenotype switching in melanoma could potentially be avoided by careful selection of target antigen.

No MeSH data available.


Related in: MedlinePlus