PURPOSE: Chemokines influence both tumor progression and anti-tumor immune response. A 32-bp-deletion polymorphism in the chemokine receptor 5 gene (CCR5Delta32) has been shown to result in a non-functional protein. This study was aimed at evaluating the potential impact of this gene polymorphism on disease progression and treatment outcome in patients with melanoma. PATIENTS AND METHODS: CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanoma patients with known disease history and long-term clinical follow-up. Genotypes were correlated with patient survival and types of treatment. RESULTS: Of 782 melanoma patients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Delta32. Analyzing the complete cohort, the disease-specific survival from date of primary diagnosis was not influenced by CCR5 status. Similarly, no significant impact could be detected on the treatment outcome of stage III patients. In 139 stage IV patients receiving immunotherapy, CCR5Delta32 was associated with a decreased survival compared to patients not carrying the deletion (median 12.5 vs. 20.3 months, P = 0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in this patient population (P = 0.002), followed by gender (P = 0.019) and pathological classification of the primary (pT; P = 0.022). CONCLUSION: The presence of the CCR5Delta32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy and may help to select patients less likely to benefit from this type of treatment.
PURPOSE:Chemokines influence both tumor progression and anti-tumor immune response. A 32-bp-deletion polymorphism in the chemokine receptor 5 gene (CCR5Delta32) has been shown to result in a non-functional protein. This study was aimed at evaluating the potential impact of this gene polymorphism on disease progression and treatment outcome in patients with melanoma. PATIENTS AND METHODS: CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanomapatients with known disease history and long-term clinical follow-up. Genotypes were correlated with patient survival and types of treatment. RESULTS: Of 782 melanomapatients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Delta32. Analyzing the complete cohort, the disease-specific survival from date of primary diagnosis was not influenced by CCR5 status. Similarly, no significant impact could be detected on the treatment outcome of stage III patients. In 139 stage IV patients receiving immunotherapy, CCR5Delta32 was associated with a decreased survival compared to patients not carrying the deletion (median 12.5 vs. 20.3 months, P = 0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in this patient population (P = 0.002), followed by gender (P = 0.019) and pathological classification of the primary (pT; P = 0.022). CONCLUSION: The presence of the CCR5Delta32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy and may help to select patients less likely to benefit from this type of treatment.
Authors: Ravikumar Muthuswamy; Erik Berk; Beth Fallert Junecko; Herbert J Zeh; Amer H Zureikat; Daniel Normolle; The Minh Luong; Todd A Reinhart; David L Bartlett; Pawel Kalinski Journal: Cancer Res Date: 2012-05-16 Impact factor: 12.701
Authors: Denarda Dangaj; Marine Bruand; Alizée J Grimm; Catherine Ronet; David Barras; Priyanka A Duttagupta; Evripidis Lanitis; Jaikumar Duraiswamy; Janos L Tanyi; Fabian Benencia; Jose Conejo-Garcia; Hena R Ramay; Kathleen T Montone; Daniel J Powell; Phyllis A Gimotty; Andrea Facciabene; Donald G Jackson; Jeffrey S Weber; Scott J Rodig; Stephen F Hodi; Lana E Kandalaft; Melita Irving; Lin Zhang; Periklis Foukas; Sylvie Rusakiewicz; Mauro Delorenzi; George Coukos Journal: Cancer Cell Date: 2019-06-10 Impact factor: 31.743
Authors: Hideaki Tahara; Marimo Sato; Magdalena Thurin; Ena Wang; Lisa H Butterfield; Mary L Disis; Bernard A Fox; Peter P Lee; Samir N Khleif; Jon M Wigginton; Stefan Ambs; Yasunori Akutsu; Damien Chaussabel; Yuichiro Doki; Oleg Eremin; Wolf Hervé Fridman; Yoshihiko Hirohashi; Kohzoh Imai; James Jacobson; Masahisa Jinushi; Akira Kanamoto; Mohammed Kashani-Sabet; Kazunori Kato; Yutaka Kawakami; John M Kirkwood; Thomas O Kleen; Paul V Lehmann; Lance Liotta; Michael T Lotze; Michele Maio; Anatoli Malyguine; Giuseppe Masucci; Hisahiro Matsubara; Shawmarie Mayrand-Chung; Kiminori Nakamura; Hiroyoshi Nishikawa; A Karolina Palucka; Emanuel F Petricoin; Zoltan Pos; Antoni Ribas; Licia Rivoltini; Noriyuki Sato; Hiroshi Shiku; Craig L Slingluff; Howard Streicher; David F Stroncek; Hiroya Takeuchi; Minoru Toyota; Hisashi Wada; Xifeng Wu; Julia Wulfkuhle; Tomonori Yaguchi; Benjamin Zeskind; Yingdong Zhao; Mai-Britt Zocca; Francesco M Marincola Journal: J Transl Med Date: 2009-06-17 Impact factor: 5.531