Abstract

CANCERIMMUNOLOGYRESEARCHPROGRAM PROGRAMCODE:CI PROJECTSUMMARY/ABSTRACT TheoverarchingmissionoftheCancerImmunology(CI)ResearchProgramistoimproveunderstandingofthe hostresponsetocancerandtodiscoverandtestnovelapproachestoharnessthatresponsetoimprove patientoutcomes.Theprogramwasrankedoutstandinginthelastrenewal.Drs.DhodapkarandChenlead theCIprogramandareexperiencedinvestigatorswitha>15-yearhistoryofsustainedNCIfundingand multiplecontributionsincancerimmunology.Dr.ChenpioneeredthetargetingofthePD-1/PD-L1pathwayin cancer,whichhastransformedcancerimmunotherapy.CIconsistsof33membersfrom8different departmentswhoseworkrevolvesaroundfourmajoraims:1)understandthemechanismsunderlyingthe capacityoftheimmunesystemtoinhibittumorgrowth,aswellasmechanismsthatdrivetumorimmune resistance;?2)discoverandtestnewapproachesforpromotinganti-tumorimmunity;?3)studythemechanistic linksbetweeninflammationandcancer;?and4)undertaketargetedtherapeutictrialsthatutilizenovelendpoint assessmentandbuildonthefundamentaldiscoveriesofAims1-3.CIexperienceda15%increaseintotal funding($12Mdirect),aswellasa21%increaseinNCIfunding($2.3Mdirect).Collaborationsremain strongwith17%intra-and30%inter-programmaticpublications. TranslationaleffortsintheCIprogramareabundant,inparticularwithourtumorimmuno-oncology(TIL)lab. MajorcollaborationsexistwiththeLungCancerSPOREandSU2Cefforts(DT),theGU/Bladdergroup(ST), thePhaseIteam(DT),HeadandNeckCancers(DT),andthecolorectalcancerSU2Ccollaborative(CPC). SamplesarebeinganalyzedinnumerousCIclinicaltrialstoinvestigatethemechanismsunderlyingresistance andresponsetoimmunetherapies.Humantissuehasbeencollectedundermultipleprotocolsandusedfor patient-derivedxenograft(PDX)andhumanizedmodels. Duringthelastfundingperiod,immunecheckpointblockadeforcancertreatmenthasemergedasoneofthe mostexcitingandpromisingnewapproachestotreatcancerindecades.CIhasplayedaleadingrolein bringingthisrevolutionaryapproachintotheclinicwithseveralseminalstudiesthatintroducedcheckpoint blockadetargetingthePD1/PD-L1pathwayinthetherapyofmelanoma,lung,gastric,head/neck,andbladder cancer.YCChasbeenattheforefrontoftheimmuno-oncologyrevolution,playingleadrolesintheearliest studiesand,eventually,FDAapprovalsofimmunecheckpointblockadeandcombinationblockade,the identificationofnewcheckpointinhibitortargets,thedevelopmentofuniqueanimalmodels,andimportant advancesinbasicimmunobiology,especiallyinT-cellbiology.Overthelastfiveyears,thegrowthofour clinicaltrialeffortsinthisareahasenabledreversetranslationusingclinicalspecimens,whichbolstersSPORE andothermulti-PIgrants.CIwillcontinueasahighlyinteractiveprogramdedicatedtoimprovingunderstanding ofthehostresponsetocanceranddevelopingnovelapproachestoimproveoutcomes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016359-40
Application #
9772267
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
40
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Ventura, Alessandra; Vassall, Aaron; Robinson, Eve et al. (2018) Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anticancer Immunity. Cancer Res 78:4045-4058
Xiao, Qian; Wu, Jibo; Wang, Wei-Jia et al. (2018) DKK2 imparts tumor immunity evasion through ?-catenin-independent suppression of cytotoxic immune-cell activation. Nat Med 24:262-270
Jagannath, Sundar; Laubach, Jacob; Wong, Ellice et al. (2018) Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study. Br J Haematol 182:495-503
Liu, Xiaoni; Zhang, Shang-Min; McGeary, Meaghan K et al. (2018) KDM5B Promotes Drug Resistance by Regulating Melanoma Propagating Cell Subpopulations. Mol Cancer Ther :
Chae, Wook-Jin; Bothwell, Alfred L M (2018) Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside. Front Immunol 9:303
Kim, Hanseul; Keum, NaNa; Giovannucci, Edward L et al. (2018) Garlic intake and gastric cancer risk: Results from two large prospective US cohort studies. Int J Cancer 143:1047-1053
Sarma, Elizabeth A; Kawachi, Ichiro; Poole, Elizabeth M et al. (2018) Social integration and survival after diagnosis of colorectal cancer. Cancer 124:833-840
Hartman, Douglas J; Ahmad, Fahad; Ferris, Robert L et al. (2018) Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma. Oral Oncol 86:278-287
Chen, Ling; Azuma, Takeshi; Yu, Weiwei et al. (2018) B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proc Natl Acad Sci U S A 115:3126-3131
Zhang, Jinhua; Song, Kun; Wang, Jun et al. (2018) S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology without disruption of antitumor immunity. Oncoimmunology 7:e1296996

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