Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion

Jiang, Yuanyuan; Zhan, Hanxiang

doi:10.1016/j.canlet.2019.10.013

Cited by 238 publications

(203 citation statements)

References 123 publications

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“…The communication between EMT and PD-L1 expression in cancer cells, as was also found in other studies [44,45,80,81], is bidirectional, in which EMT transcription factors up-regulate the expression of PD-L1, while the latter, in turn, can promote the EMT process. This complex relationship between EMT and PD-L1 signaling plays an important role in the immune evasion of the tumors [80]. On the other hand, these findings may suggest that cisplatin-resistant EMT tumor cells could display an increased sensitivity to anti-PD-1 or anti-PD-L1 antibody treatment [82].…”

Section: Interaction With An Inflammatory Microenvironmentsupporting

confidence: 76%

“…In lung adenocarcinomas with an EMT phenotype, the co-existence of immune activation with the elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, together with an increase in their infiltration by CD4 + Foxp3 + regulatory T cells, was observed [79]. The communication between EMT and PD-L1 expression in cancer cells, as was also found in other studies [44,45,80,81], is bidirectional, in which EMT transcription factors up-regulate the expression of PD-L1, while the latter, in turn, can promote the EMT process. This complex relationship between EMT and PD-L1 signaling plays an important role in the immune evasion of the tumors [80].…”

Section: Interaction With An Inflammatory Microenvironmentsupporting

confidence: 72%

See 1 more Smart Citation

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Dudás

Ladányi

Ingruber

et al. 2020

Cells

130

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Epithelial to mesenchymal transition (EMT) contributes to tumor progression, cancer cell invasion, and therapy resistance. EMT is regulated by transcription factors such as the protein products of the SNAI gene family, which inhibits the expression of epithelial genes. Several signaling pathways, such as TGF-beta1, IL-6, Akt, and Erk1/2, trigger EMT responses. Besides regulatory transcription factors, RNA molecules without protein translation, micro RNAs, and long non-coding RNAs also assist in the initialization of the EMT gene cluster. A challenging novel aspect of EMT research is the investigation of the interplay between tumor microenvironments and EMT. Several microenvironmental factors, including fibroblasts and myofibroblasts, as well as inflammatory, immune, and endothelial cells, induce EMT in tumor cells. EMT tumor cells change their adverse microenvironment into a tumor friendly neighborhood, loaded with stromal regulatory T cells, exhausted CD8+ T cells, and M2 (protumor) macrophages. Several EMT inhibitory mechanisms are instrumental in reversing EMT or targeting EMT cells. Currently, these mechanisms are also significant for clinical use.

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Section: Interaction With An Inflammatory Microenvironmentsupporting

confidence: 76%

Section: Interaction With An Inflammatory Microenvironmentsupporting

confidence: 72%

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Dudás

Ladányi

Ingruber

et al. 2020

Cells

130

View full text Add to dashboard Cite

show abstract

“…PD-L1 can be expressed on immature tumor-associated dendritic cells, negatively affecting their functions. PD-L1 can be also expressed by tumor endothelial cells, producing an immunosuppressive environment, and by tumor cells themselves, blocking CTL activity and tumor rejection [9]. Cytokines and chemokines produced by tumor cells can inhibit T lymphocyte crossing of the tumor vasculature by reducing endothelial cell expression of adhesion molecules, while functioning as chemoattractants for immunosuppressive leukocytes such as T regulatory cells, Tie2+ monocytes, or myeloid-derived suppressor cells.…”

Section: Introductionmentioning

confidence: 99%

Melanoma and Vitiligo: In Good Company

Failla

Carbone

Fortes

et al. 2019

IJMS

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Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin melanocytes. However, vitiligo has been associated with cutaneous melanoma since the 1970s. Most of the antigens recognized by the immune system are expressed by both melanoma cells and normal melanocytes, explaining why the autoimmune response against melanocytes that led to vitiligo could be also present in melanoma patients. Leukoderma has been also observed as a side effect of melanoma immunotherapy and has always been associated with a favorable prognosis. In this review, we discuss several characteristics of the immune system responses shared by melanoma and vitiligo patients, as well as the significance of occurrence of leukoderma during immunotherapy, with special attention to check-point inhibitors.

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“…Besides playing an essential role in immunosuppression and a possible role in resistance to immunotherapy as discussed previously, 356 it is interesting to note that the "bidirectional regulation between EMT and PD-L1" is also involved in resistance to targeted therapy 357 as well as chemotherapy, linking it to functions beyond its immunoregulation activities. Researchers have demonstrated that upregulation of PD-L1 mediated by YAP at the transcript level leads to the acquired resistance to EGFR-TKIs (e.g., gefitinib) in NSCLC, a process that largely depends on the induction of EMT.…”

Section: Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 95%

Emerging role of tumor cell plasticity in modifying therapeutic response

Qin

Jiang

Lü

et al. 2020

Sig Transduct Target Ther

156

122

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Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here. Such non-mutational processes are largely driven by tumor cell plasticity, which renders tumor cells insusceptible to the drug-targeted pathway, thereby facilitating the tumor cell survival and growth. The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition, acquisition properties of cancer stem cells, and trans-differentiation potential during drug exposure. From observations in various cancers, this concept provides an opportunity for investigating the nature of anticancer drug resistance. Over the years, our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased. This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs, which are likely to improve patient outcomes in clinical practice.

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Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion

Cited by 238 publications

References 123 publications

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Melanoma and Vitiligo: In Good Company

Emerging role of tumor cell plasticity in modifying therapeutic response

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