A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Huang, Alexander C.; Zappasodi, Roberta

doi:10.1038/s41590-022-01141-1

Cited by 309 publications

(252 citation statements)

References 151 publications

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“…Melanoma is the most lethal skin cancer with increasing incidence worldwide over the past several decades ( Muzumdar et al, 2021 ; Welch et al, 2021 ; Huang and Zappasodi, 2022 ). It has multiple risk factors involved in the interaction between genetic susceptibility and environmental exposure ( Rastrelli et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma), arising from the malignant transformation of melanocytes, is the most aggressive and deadliest type of skin cancer ( Huang and Zappasodi, 2022 ). Although it accounts for about 1% of all skin cancers, it is responsible for about 80% of the deaths from these skin cancers ( Banach et al, 2021 ; Moyers and Glitza Oliva, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…The interaction between genetic susceptibility and environmental exposures contributes to the onset and development of melanoma ( Dzwierzynski, 2021 ). Ultraviolet exposure and high tumor mutation burden are supposed to be the most common risk factors in melanoma ( Huang and Zappasodi, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

et al. 2022

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Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) is the most lethal skin cancer with increasing incidence. Regulated cell death plays an important role in tumorigenesis and serves as an important target for almost all treatment strategies. Cuproptosis is the most recently identified copper-dependent regulated cell death form that relies on mitochondria respiration. However, its role in tumorigenesis remains unknown. The correlation of cuproptosis-related genes with tumor prognosis is far to be understood, either. In the present study, we explored the correlation between cuproptosis-related genes with the prognosis of melanoma by accessing and analyzing a public database and found 11 out 12 genes were upregulated in melanoma tissues and three genes (LIPT1, PDHA1, and SLC31A1) have predictive value for the prognosis. The subgroup of melanoma patients with higher cuproptosis-related gene expression showed longer overall survival than those with lower gene expression. We chose LIPT1 for further exploration. LIPT1 expression was increased in melanoma biopsies and was an independent favorable prognostic indicator for melanoma patients. Moreover, LIPT1 expression was positively correlated with PD-L1 expression and negatively associated with Treg cell infiltration. The melanoma patients with higher LIPT1 expression showed longer overall survival than those with lower LIPT1 expression after receiving immunotherapy, indicating the prognostic predictive value of LIPT1. Finally, a pan-cancer analysis indicated that LIPT1 was differentially expressed in diverse cancers as compared to normal tissues and correlated with the expression of multiple immune checkpoints, especially PD-L1. It could serve as a favorable prognosis indicator in some cancer types. In conclusion, our study demonstrated the prognostic value of cuproptosis-related genes, especially LIPT1, in melanoma, and revealed the correlation between LIPT1 expression and immune infiltration in melanoma, thus providing new clues on the prognostic assessment of melanoma patients and providing a new target for the immunotherapy of melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

et al. 2022

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“…Immune checkpoint inhibitors (ICIs) are novel treatment options gaining more and more interest, as they already appeared to be successful strategies in cancers such as melanoma or lung cancer [90][91][92][93][94][95][96]. Among CTLA-4 inhibitors there are ipilimumab and tremelimumab, while the most pivotal PD-1 inhibitors comprise nivolumab and pembrolizumab; atezolizumab belongs to PD-L1 inhibitors [97].…”

Section: Immune Check-point Inhibitorsmentioning

confidence: 99%

Boosting the Immune Response – Combining the Local and Immune Therapy for Prostate Cancer Treatment

Karwacki¹,

Szlasa²,

Sauer³

et al. 2022

Preprint

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Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

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“…For example, in oncology, numerous attempts have been made to identify a cell type or cell state that is predictive of response to checkpoint inhibitor immunotherapy. Among the many candidates, one can find cytotoxic effector T cells, peripheral memory T helper cells, and B cells (Huang & Zappasodi, 2022 ). While it may be plausible that a response is determined by a single cell type in a particular state, an alternative and rather compelling hypothesis is that the interaction of different cells in diverse states is what drives complex phenotypes such as a response to treatment.…”

mentioning

confidence: 99%

From genes to modules, from cells to ecosystems

Haran

Keren

2022

Molecular Systems Biology

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Twenty years ago, molecular biology transitioned from predominantly studying genes as isolated elements to viewing them as part of complex modules, giving rise to the field of systems biology. This transition was made possible by technological advances that allowed to simultaneously measure the expression levels of thousands of genes in a single experiment and drove a shift toward analyses identifying gene sets, modules, and pathways involved in a biological process of interest. Today we are excitingly facing a similar turning point in cell biology, where single‐cell technologies have enabled us to approach cells as cellular modules.

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A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Cited by 309 publications

References 151 publications

Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

Boosting the Immune Response – Combining the Local and Immune Therapy for Prostate Cancer Treatment

From genes to modules, from cells to ecosystems

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