New combinations and immunotherapies for melanoma: latest evidence and clinical utility

Menzies, Alexander M.; Long, Georgina V.

doi:10.1177/1758834013499637

Cited by 25 publications

(19 citation statements)

References 31 publications

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“…Immune checkpoint inhibitors are revolutionizing the ability to treat metastatic cancer (15)(16)(17)(18). Many clinical trials are under way using these agents to treat a variety of cancers, and inhibitors of CTLA-4 and PD-1 have been approved for melanoma (19).…”

Section: Discussionmentioning

confidence: 99%

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

Al‐Omari

Cohen

Vortmeyer

et al. 2016

Cancer Immunology Research

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Delayed radiation-induced vasculitic leukoencephalopathy related to stereotactic radiosurgery (SRS) of brain metastases has been reported to manifest clinically 9 to 18 months after treatment. Immune-modulating therapies have been introduced to treatment regimens for malignancies with metastatic predilection to the brain. The interaction of these systemic therapies with other modalities of treatment for brain metastases, namely, SRS, has not been fully characterized. We report two patients with metastatic malignancies to the brain who received SRS followed by immunotherapy with monoclonal antibodies (mAb) to programmed death 1 (PD-1). Both patients appeared to have early clinical and radiologic progression of their treated lesions, which was highly suspicious for tumor progression. Both patients underwent surgical resection of their lesions and the material was submitted for histopathologic examination. Pathologic examination in both cases showed predominantly radiation-induced changes characterized by reactive astrocytosis and vascular wall infiltration by T lymphocytes. The accelerated response to SRS in these two patients was temporally related to the initiation of immunotherapy. We propose a possible biologic interaction between SRS and the PD-1 mAbs. Additionally, awareness of this potential occurrence is critical for accurate interpretation and proper management of clinical and radiologic findings in these patients.

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Section: Discussionmentioning

confidence: 99%

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

Al‐Omari

Cohen

Vortmeyer

et al. 2016

Cancer Immunology Research

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“…Here we focused on the potential role of immunotherapy as an alternative therapeutic strategy, one that has been used with some success in melanoma (11,41). Next to nothing is known about the effects of the signaling pathway alterations seen in differentiated thyroid cancers on the immune antigens of the thyroid cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…There have been several advances in immunotherapeutic strategies over recent years especially in treating melanoma (10,11); however, immunotherapy as a treatment for thyroid cancer has not been well studied.…”

Section: Introductionmentioning

confidence: 99%

A Potential Role for Immunotherapy in Thyroid Cancer by Enhancing NY-ESO-1 Cancer Antigen Expression

Gunda

Frederick

Bernasconi

et al. 2014

Thyroid

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Background: NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells. Methods: We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2¢-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2 +, NY-ESO-1 + thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo. Results: None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells. Conclusion: Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions.

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“…Targeting either PD-1 or PD-L1 can stimulate the immune system and enhance the T-cells' ability to lyse tumor cells. This axis could also be a very promising therapeutic target for mucosal melanoma as patients with cutaneous melanoma, who participated in recent studies and were administered antibodies against the PD-1/PD-L1 pathway, showed high response rates with longer survival [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck

Thierauf¹,

Veit²,

Affolter

et al. 2015

Melanoma Research

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Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpression of the programmed cell death ligand 1 (PD-L1) is a common feature in human cancer. Although PD-L1 is an acknowledged prognostic biomarker for dismal prognosis in other tumors of the head and neck, expression and clinical relevance of PD-L1 in mucosal melanoma have not been addressed so far. We assessed PD-L1 expression using immunohistochemical staining in 23 tumor samples from patients with primary mucosal melanoma and correlated expression status with clinicopathological and outcome data. Tumors were derived from the nasal cavity (43.5%), nasal sinuses (43.5%), and the conjunctiva (13%). All patients had undergone surgery; 39% of all patients received adjuvant radiation and 13% were administered systemic interferon therapy. The probability of 1- and 5-year overall survival was 87 and 34.8%, respectively. The mean overall survival was 51 months and the mean recurrence-free survival was 23 months. Immunohistochemical staining showed PD-L1 expression in 13% (3/23) of mucosal melanoma. In contrast, prominent PD-L1 staining was detected in 100% of tissue sections from a control group of cutaneous melanoma (n=9). PD-L1 expression in mucosal melanoma was not correlated with age, sex, nor anatomical localization of the tumor. Interestingly, patients with PD-L1-positive mucosal melanoma had a significantly longer recurrence-free survival (P=0.026). In contrast to cutaneous melanoma and some other malignancies, a relevant PD-L1 overexpression in mucosal melanoma could not be confirmed.

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New combinations and immunotherapies for melanoma: latest evidence and clinical utility

Cited by 25 publications

References 31 publications

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

A Potential Role for Immunotherapy in Thyroid Cancer by Enhancing NY-ESO-1 Cancer Antigen Expression

Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck

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