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 #
3P30CA016359-39S1
Application #
9772315
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Roberson, Sonya
Project Start
Project End
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
39
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

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

  Publications

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
Kelada, Olivia J; Decker, Roy H; Nath, Sameer K et al. (2018) High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors. Int J Radiat Oncol Biol Phys 102:174-183
Powles, Ryan L; Redmond, David; Sotiriou, Christos et al. (2018) Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncol 4:e181564
Wang, Shi-Yi; Hsu, Sylvia H; Huang, Siwan et al. (2018) Regional Practice Patterns and Racial/Ethnic Differences in Intensity of End-of-Life Care. Health Serv Res 53:4291-4309
Gettinger, S N; Choi, J; Mani, N et al. (2018) A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nat Commun 9:3196
Liu, Huafeng; Li, Xin; Hu, Li et al. (2018) A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma. Cell Mol Immunol 15:838-845
Altwerger, Gary; Bonazzoli, Elena; Bellone, Stefania et al. (2018) In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. Mol Cancer Ther 17:1003-1011

Showing the most recent 10 out of 675 publications