Immunotherapy in Melanoma

Feld, Emily; Mitchell, Tara C.

doi:10.2217/imt-2017-0143

Cited by 25 publications

(16 citation statements)

References 51 publications

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“…Immunotherapy is another expanding area of melanoma treatment research. In its initial stages, melanoma is known to be the most immunogenic type of cancer [38,39], although this feature is lost when melanoma reaches the metastatic state, manipulating the microenvironment and abolishing the immune responses [40]. Between 1985 and 1993, research on immunotherapy with interleukin-2 (IL-2), a cytokine that promotes T cell growth, greatly progressed, with its approval by the Food and Drug Administration (FDA), in 1998, as the first immunotherapy for advanced melanoma [32,39].…”

Section: Melanoma—general Overviewmentioning

confidence: 99%

“…In its initial stages, melanoma is known to be the most immunogenic type of cancer [38,39], although this feature is lost when melanoma reaches the metastatic state, manipulating the microenvironment and abolishing the immune responses [40]. Between 1985 and 1993, research on immunotherapy with interleukin-2 (IL-2), a cytokine that promotes T cell growth, greatly progressed, with its approval by the Food and Drug Administration (FDA), in 1998, as the first immunotherapy for advanced melanoma [32,39]. More recently, the blockade of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1) have enhanced T-cell mediated antitumor immunity [33,39,41,42].…”

Section: Melanoma—general Overviewmentioning

confidence: 99%

“…Between 1985 and 1993, research on immunotherapy with interleukin-2 (IL-2), a cytokine that promotes T cell growth, greatly progressed, with its approval by the Food and Drug Administration (FDA), in 1998, as the first immunotherapy for advanced melanoma [32,39]. More recently, the blockade of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1) have enhanced T-cell mediated antitumor immunity [33,39,41,42]. Although the clinical data are promising, low percentages of effective and prolonged responses, resistance or relapse and adverse effects have been observed for immune checkpoint therapy [39,43,44,45].…”

Section: Melanoma—general Overviewmentioning

confidence: 99%

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Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosinase. In addition, the role of nanotechnology as a valuable strategy to effectively deliver selective drugs is emphasized, either incorporating/encapsulating synthetic molecules or natural-derived compounds in lipid-based nanosystems such as liposomes. Nanoformulated compounds have been explored for their improved anticancer activity against melanoma and promising results have been obtained. Indeed, they displayed improved physicochemical properties and higher accumulation in tumoral tissues, which potentiated the efficacy of the compounds in pre-clinical experiments. Overall, these experiments opened new doors for the discovery and development of more effective drug formulations for melanoma treatment.

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Section: Melanoma—general Overviewmentioning

confidence: 99%

Section: Melanoma—general Overviewmentioning

confidence: 99%

Section: Melanoma—general Overviewmentioning

confidence: 99%

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Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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“…Melanoma and colorectal cancer (CRC) are common cancers associated with high mortality worldwide . The management of melanoma and CRC have improved overall survival rates during the last decades, yet the majority of patients do not respond to treatment and succumb to disease progression, mainly due to upregulating the surface program death‐ligand 1 (PD‐L1) expression . Therefore, deep understanding of the PD‐L1 upregulating mechanism is urgently needed for melanoma and CRC.…”

Section: Introductionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

141

131

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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.

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“…For example, medical treatment of metastatic melanoma, urothelial cancer, non-small cell lung cancer, and renal cell carcinoma has been revolutionized in recent years, reporting unprecedented response rates and survival benefits [ 19 , 20 , 21 , 22 , 23 , 24 ]. Two meaningful examples are the impressive complete response rate of 10% achieved with nivolumab plus ipilimumab combination in metastatic renal cell carcinoma in Checkmate 214 trial and the survival benefits provided by immune checkpoint monoclonal antibodies in metastatic malignant melanoma where—until the approval of ipilimumab in 2011—patients with distant metastases presented 5-year survival rates of approximately 5% [ 25 , 26 ]. Moreover, on the basis of recent results of trials testing immunotherapy alone or in combination with other anticancer agents in different malignancies (e.g., gastric cancer, colorectal cancer, hepatocellular carcinoma, etc.)…”

Section: Predictive Biomarkers: Pd-l1 Msi Mmr Tmb Ddr Tilsmentioning

confidence: 99%

Is There a Role for Immunotherapy in Prostate Cancer?

Rizzo

Mollica

Cimadamore

et al. 2020

Cells

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In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.

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Immunotherapy in Melanoma

Cited by 25 publications

References 51 publications

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Is There a Role for Immunotherapy in Prostate Cancer?

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