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 #
3P30CA016359-39S3
Application #
9772317
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

Bonazzoli, Elena; Predolini, Federica; Cocco, Emiliano et al. (2018) Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clin Cancer Res 24:4845-4853
Villarroel-Espindola, Franz; Yu, Xiaoqing; Datar, Ila et al. (2018) Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non-Small Cell Lung Cancer. Clin Cancer Res 24:1562-1573
Wadia, Roxanne J; Stolar, Marilyn; Grens, Clarice et al. (2018) The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients. Oncotarget 9:7322-7331
De Feyter, Henk M; Behar, Kevin L; Corbin, Zachary A et al. (2018) Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo. Sci Adv 4:eaat7314
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

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