Melanoma immunotherapy: strategies to overcome pharmacological resistance

Trojaniello, Claudia; Vitale, Maria Grazia; Scarpato, Luigi; Esposito, Assunta; Ascierto, Paolo A.

doi:10.1080/14737140.2020.1745634

Cited by 15 publications

(13 citation statements)

References 178 publications

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“…Indoleamine-2,3-dioxygenase (IDO) is an enzyme that lowers the level of tryptophan, induces cell-cycle arrest and effector T-cell apoptosis, and promotes Treg activity [199]. The presence of IDO in the tumor microenvironment is considered a possible mechanism of resistance to immunotherapy and IDO inhibitors (epacadostat and indoximod) have been combined with ipilimumab, nivolumab, or pembrolizumab in melanoma [200], but not so far in CSCC.…”

Section: Other Combinationsmentioning

confidence: 99%

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

García-Sancha

Corchado-Cobos

Bellido-Hernández

et al. 2021

Cancers

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Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, and is now responsible for as many deaths as melanoma. Immunotherapy has changed the therapeutic landscape of advanced CSCC after the FDA approval of anti-PD1 molecules for the treatment of locally advanced and metastatic CSCC. However, roughly 50% of patients will not respond to this systemic treatment and even those who do respond can develop resistance over time. The etiologies of primary and secondary resistance to immunotherapy involve changes in the neoplastic cells and the tumor microenvironment. Indirect modulation of immune system activation with new therapies, such as vaccines, oncolytic viruses, and new immunotherapeutic agents, and direct modulation of tumor immunogenicity using other systemic treatments or radiotherapy are now under evaluation in combined regimens. The identification of predictors of response is an important area of research. In this review, we focus on the features associated with the response to immunotherapy, and the evaluation of combination treatments and new molecules, a more thorough knowledge of which is likely to improve the survival of patients with advanced CSCC.

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Section: Other Combinationsmentioning

confidence: 99%

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

García-Sancha

Corchado-Cobos

Bellido-Hernández

et al. 2021

Cancers

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“…Nevertheless, regardless of the groundbreaking treatment options, most patients invariably relapse from BRAF/ MEK signaling inhibition within a year from treatment commencement (6). About 50% of patients treated with immune checkpoints inhibitors do not respond due to primary resistance and a great proportion of responders experience tumor relapse within 2 years (7,8). Current 5-year survival rate for metastatic melanoma is therefore 27% (9).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells

et al. 2021

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Regardless of the recent groundbreaking introduction of personalized therapy, melanoma continues to be one of the most lethal skin malignancies. Still, a substantial proportion of patients either fail to respond to the therapy or will relapse over time, representing a challenging clinical problem. Recently, we have shown that vitamin D enhances the effectiveness of classical chemotherapeutics in the human malignant melanoma A375 cell line. In search for new combination strategies and adjuvant settings to improve melanoma patient outcomes in the current study, the effects of cediranib (AZD2171), an oral tyrosine kinase inhibitor of VEGFR1-3, PDGFR, and c-KIT, used in combination either with 1,25(OH)2D3 or with low-calcemic analog calcipotriol were tested on four human malignant melanoma cell lines (A375, MNT-1, RPMI-7951, and SK-MEL-28). Melanoma cells were pretreated with vitamin D and subsequently exposed to cediranib. We observed a marked decrease in melanoma cell proliferation (A375 and SK-MEL-28), G2/M cell cycle arrest, and a significant decrease in melanoma cell mobility in experimental conditions used (A375). Surprisingly, concurrently with a very desirable decrease in melanoma cell proliferation and mobility, we noticed the upregulation of VEGFR2 at both protein and mRNA levels. No effect of vitamin D was observed in MNT-1 and RPMI-7951 melanoma cells. It seems that vitamin D derivatives enhance cediranib efficacy by modulation of VEGFR2 expression in melanoma cells expressing VEGFR2. In conclusion, our experiments demonstrated that vitamin D derivatives hold promise as novel adjuvant candidates to conquer melanoma, especially in patients suffering from vitamin D deficiency. However, further extensive research is indispensable to reliably assess their potential benefits for melanoma patients.

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“…Many approaches are currently under investigation aiming to surmount resistance to ICIs and improve clinical outcomes, often focusing on combining various therapeutic modalities (traditional therapies, other immunotherapy regiments as well as molecularly targeted therapies) on a checkpoint inhibitor backbone [ 257 ]. From a mechanism point of view, ongoing approaches aim to promote antigen processing and presentation, improve tumor antigen release and neoantigen supply, enhance T cell priming, expansion, survival, and effector functions, make the TME more friendly for immune cells, attenuate tumor-induced immunosuppressive factors, and promote proinflammatory/immunogenic pathways [ 258 , 259 , 260 ]. Moreover, there is significant evidence that gut microbiota diversity and composition can affect ICI responses and resistance in many cancers, by educating local and systemic immune responses, enhancing beneficial effects of metabolites, and dampening immune-related side-effects [ 261 ].…”

Section: Strategies For Enhancing Ici Therapy Effectiveness: the mentioning

confidence: 99%

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Mpakali

Stratikos

2021

Cancers

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Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

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Melanoma immunotherapy: strategies to overcome pharmacological resistance

Cited by 15 publications

References 178 publications

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

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