Diversity and Recognition Efficiency of T Cell Responses to Cancer 英文参考文献.docVIP

o Openaccess,freelyavailableonline PL S MEDICINE DiversityandRecognitionEfficiency ofTCellResponsestoCancer Tor B.Stuge1,Susan P.Holmes2,Sahdev Saharan1,Andrea Tuettenberg3,Mario Roederer4,Jeffrey S.Weber5, Peter P.Lee1* 1Department of Medicine, Division of Hematology, Stanford University, Stanford, California, United States of America, 2Department of Statistics, Stanford University, Stanford, California, United StatesofAmerica,3Department ofDermatology,J.Gutenberg-University, Mainz, Germany, 4ImmunoTechnologySection,Vaccine Research Center,NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,5NorrisCancerCenter,Universityof SouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica ABSTRACT CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. Background AuthorContributions:TBS,SS, MR,andPPLdesignedthestudy. TBS,SPH,SS,MR,JSW,andPPL analyzedthedata.MRprovided keyvalidatedreagentsforthe study.ATandJSWenrolledpa- tients.TBS,SPH,SS,AT,MR,JSW, andPPLcontributedtowritingthe paper. Melanoma patients vaccinated with tumor-associated antigens frequently develop mea- surablepeptide-specificCD8tTcellresponses;however,suchresponsesoftendonotconfer clinicalbenefit.Understandingwhyvaccine-elicitedresponsesarebeneficialinsomepatients butnotinotherswillbeimportanttoimprovetargetedcancerimmunotherapies. MethodsandFindings AcademicEditor:PhilippaMar- rack,NationalJewishMedicaland ResearchCenter/HowardHughes MedicalInstitute,UnitedStatesof America We analyzed peptide-specific CD8t T cell responses in detail, by generating and characterizing over 200 cytotoxic T lymphocyte clones derived from T cell responses to heterocliticpeptidevaccination,andcomparedtheseresponsestoendogenousanti-tumorT cell responses elicited naturally (a heteroclitic peptide is a modification of a native peptide sequence involving substitution of an amino acid at an anchor residue to enhance the immunogenicity of