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 #
3P30CA016359-40S1
Application #
9989662
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
He, Min
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
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Sanmamed, Miguel F; Chen, Lieping (2018) A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 175:313-326
Gupta, Swati; Mani, Navin R; Carvajal-Hausdorf, Daniel E et al. (2018) Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Lab Invest 98:1076-1083
Bellone, Stefania; Buza, Natalia; Choi, Jungmin et al. (2018) Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clin Cancer Res 24:3282-3291
Altan, Mehmet; Kidwell, Kelley M; Pelekanou, Vasiliki et al. (2018) Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer. NPJ Breast Cancer 4:40
Kim, Tae Kon; Herbst, Roy S; Chen, Lieping (2018) Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends Immunol 39:624-631
Goldberg, Sarah B; Patel, Abhijit A (2018) Monitoring immunotherapy outcomes with circulating tumor DNA. Immunotherapy 10:1023-1025
Wang, Shi-Yi; Long, Jessica B; Killelea, Brigid K et al. (2018) Associations of preoperative breast magnetic resonance imaging with subsequent mastectomy and breast cancer mortality. Breast Cancer Res Treat 172:453-461
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

Showing the most recent 10 out of 675 publications