N Engl J Med · 2014

Genetic basis for clinical response to CTLA-4 blockade in melanoma

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA.

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  • Snyder ADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Makarov VDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Merghoub TDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Yuan JDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Zaretsky JMDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Desrichard ADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Walsh LADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Postow MADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Wong PDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Ho TSDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Hollmann TJDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Bruggeman CDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Kannan KDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Li YDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Elipenahli CDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Liu CDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Harbison CTDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Wang LDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Ribas ADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Wolchok JDDepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
  • Chan TADepartment of Medicine (A.S., T.M., M.A.P., J.D.W.), Human Oncology and Pathogenesis Program (A.S., V.M., A.D., L.A.W., K.K., T.A.C.), Swim across America-Ludwig Collaborative Research Laboratory (T.M., Y.L., C.E., C.L., J.D.W.), Department of Radiation Oncology (T.A.C.), Department of Pathology (T.J.H.), and Immunology Program, Ludwig Center for Cancer Immunotherapy (J.Y., P.W., T.S.H., J.D.W.), Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College (A.S., M.A.P., J.D.W., T.A.C.); and Department of Mathematics, Columbia University (C.B.) - all in New York; the Department of Molecular and Medical Pharmacology (J.M.Z., A.R.) and the Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (A.R.), University of California, Los Angeles, Los Angeles; and Bristol-Myers Squibb, Princeton, NJ (C.T.H., L.W.).
42 read8 want to readRigor 2.6Novelty 3.2Impact 3.3Reprod. 2.7

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Discussion

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0

Lena Nguyen

Rigor 4/5Novelty 4/5Impact 5/5Reprod. 1/5

Solid methods, convincing results.

0

Ravi Rossi

Rigor 5/5Novelty 3/5Impact 1/5Reprod. 3/5

Solid methods, convincing results.

0

Hugo Brown

Rigor 2/5Novelty 1/5Impact 2/5Reprod. 4/5

Replication is unclear to me.

0

Yuki Silva

Rigor 3/5Novelty 5/5Impact 5/5Reprod. 1/5

Nice but incremental.

0

Hugo Park

Rigor 5/5Novelty 2/5Impact 3/5Reprod. 4/5

Nice but incremental.

0

Ines Park

Rigor 1/5Novelty 1/5Impact 3/5Reprod. 4/5

Interesting idea, small sample.

0

Ravi Mueller

Rigor 3/5Novelty 3/5Impact 3/5Reprod. 3/5

Solid methods, convincing results.

0

Eva Garcia

Rigor 3/5Novelty 5/5Impact 5/5Reprod. 3/5

Replication is unclear to me.

0

Nadia Sato

Rigor 1/5Novelty 3/5Impact 3/5Reprod. 4/5

Solid methods, convincing results.