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Revisiting the mechanisms of PTEN loss in melanoma [Meeting Abstract]
Giles, Keith; Li, Yang; Salhi, Amel; Wang, Jinhua; Robinson, Eric; Osman, Iman
ISI:000371578504269
ISSN: 1538-7445
CID: 2056842
Integration of melanoma genotyping in clinical care [Meeting Abstract]
Salhi, Amel; Da Silva, Ines Pires; Lui, Kevin P; Ismaili, Naima; Wu, Chaowei; de Miera, Eleazar CVega-Saenz; Shapiro, Richard L; Berman, Russell S; Pavlick, Anna C; Zhong, Judy; Heguy, Adriana; Osman, Iman
ISI:000370972700025
ISSN: 1538-7445
CID: 2029792
Association between TERT promoter mutations and BRAF/NRAS mutations in patients with primary and metastatic melanoma tumors [Meeting Abstract]
Chang, Gregory A; Tadepalli, Jyothirmayee S; Fleming, Nathaniel H; Lui, Kevin; Shao, Yongzhao; Darvishian, Farbod; Pavlick, Anna; Berman, Russell; Shapiro, Richard; Osman, Iman; Polsky, David
ISI:000370972700021
ISSN: 1538-7445
CID: 2029702
Hyperactivation of RSK1 is a hallmark of metastatic nodular melanoma [Meeting Abstract]
Salhi, Amel; Farhadian, Joshua A; Giles, Keith M; de Miera, Eleazar CVega-Saenz; Da Silva, Ines Pires; Bourque, Caitlin; Yeh, Karen; Chhangawala, Sagar; Wang, Jinhua; Ye, Fei; Zhang, David Y; Hernando-Monge, Eva; Houvras, Yariv; Osman, Iman
ISI:000370972700009
ISSN: 1538-7445
CID: 2029692
The expression and methylation quantitative trait loci (eQTLs and mQTLs) predict melanoma clinical outcomes [Meeting Abstract]
Kirchhoff, T; Vogelsang, M; Martinez, CN; Hecht, C; Tella, A; Shapiro, RL; Berman, RS; Osman, I
ISI:000361887403195
ISSN: 1879-0852
CID: 1812602
Melanoma expression of matrix metalloproteinase-23 is associated with blunted tumor immunity and poor responses to immunotherapy
Moogk, Duane; da Silva, Ines; Ma, Michelle W; Friedman, Erica B; de Miera, Eleazar; Darvishian, Farbod; Scanlon, Patrick; Perez-Garcia, Arianne; Pavlick, Anna C; Bhardwaj, Nina; Christos, Paul J; Osman, Iman; Krogsgaard, Michelle
BackgroundMatrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.MethodsWe characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P inverted question mark= inverted question mark0.05), in particular brisk TILs (P inverted question mark= inverted question mark0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P inverted question mark= inverted question mark0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P inverted question mark= inverted question mark0.037) but not in those treated with vaccines (P inverted question mark= inverted question mark0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P inverted question mark= inverted question mark0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P inverted question mark= inverted question mark0.27).ConclusionsOur data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.
PMCID:4272770
PMID: 25491880
ISSN: 1479-5876
CID: 1393652
Reversal of natural killer cell exhaustion by TIM-3 blockade
Gallois, Anne; Silva, Ines; Osman, Iman; Bhardwaj, Nina
Natural killer (NK) cells are innate immune cells that become progressively exhausted in advanced stage cancer, crippling their ability to execute antitumor functions. We previously characterized the nature of NK cell exhaustion in metastatic melanoma patients, reporting a correlation with high expression of TIM-3. Blockade of this immune checkpoint molecule reversed the exhausted phenotype and improved NK cell function.
PMCID:4353130
PMID: 25964857
ISSN: 2162-4011
CID: 2912072
Analysis of recurrence patterns in acral versus nonacral melanoma: should histologic subtype influence treatment guidelines?
Gumaste, Priyanka V; Fleming, Nathaniel H; Silva, Ines; Shapiro, Richard L; Berman, Russell S; Zhong, Judy; Osman, Iman; Stein, Jennifer A
Current surgical treatment of primary melanoma is uniform for all histosubtypes, although certain types of melanoma, such as acral lentiginous melanoma (ALM), have a worse prognosis. No study has explored the effectiveness of standard melanoma treatment guidelines for managing ALM compared with nonacral melanoma (NAM). Study subjects were identified from a prospectively enrolled database of patients with primary melanoma at New York University. Patients with ALM were matched to those with NAM (1:3) by gender and melanoma stage, including substage (ALM, 61; NAM, 183). All patients received standard-of-care treatment. Recurrence and survival outcomes in both cohorts were compared. ALM histologic subtype was an independent negative predictor of recurrence-free survival (hazard ratio [HR], 2.24; P=.001) and melanoma-specific survival (HR, 2.58; P=.001) compared with NAM. Recurrence was significantly more common in patients with ALM than in those with NAM (49% vs 30%; P=.007). For tumors less than 2 mm in thickness, a significantly higher recurrence rate was seen with ALM versus NAM (P=.048). No significant difference was seen in recurrence for tumors greater than 2 mm (P=.12). Notably, the rate of locoregional recurrence was nearly double for ALM compared with NAM (P=.001). The data presented herein reveal a high rate of locoregional failure in ALM compared with NAM when controlling for AJCC stage. These results raise the question of whether ALM may require more aggressive surgical treatment than nonacral cutaneous melanomas of equal thickness, particularly in tumors less than 2 mm thick. Larger multicenter trials are necessary for further conclusions.
PMCID:4469335
PMID: 25505211
ISSN: 1540-1405
CID: 1424152
Quantitative assessment of circulating BRAF DNA in stage IV melanoma patients undergoing BRAF inhibitor treatment [Meeting Abstract]
Polsky, David; Tadepalli, Jyothi Sakuntala; Chang, Gregory; Fleming, Nathaniel; Shao, Yongzhao; Pavlick, Anna C; Osman, Iman; Spittle, Cindy; Furtado, Manohar; Stonemetz, Paula; Shelton, Dawne; Karlin-Neumann, George
ISI:000349906904109
ISSN: 1538-7445
CID: 1599172
Reversal of NK cell exhaustion in advanced melanoma patients by Tim-3 blockade [Meeting Abstract]
Gallois, Anne; Da Silva, Ines Pires; Jimenez, Sonia; Osman, Iman; Bhardwaj, Nina
ISI:000349910203326
ISSN: 1538-7445
CID: 1599262