2021
The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
El Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, de Freitas JR, Sur D, Amendola LC, Gharib M, Kallala A, Arun I, Azmoudeh-Ardalan F, Fujimoto L, Sua LF, Liu SW, Lien HC, Kirtani P, Balancin M, El Attar H, Guleria P, Yang W, Shash E, Chen IC, Bautista V, Do Prado Moura JF, Rapoport BL, Castaneda C, Spengler E, Acosta-Haab G, Frahm I, Sanchez J, Castillo M, Bouchmaa N, Md Zin RR, Shui R, Onyuma T, Yang W, Husain Z, Willard-Gallo K, Coosemans A, Perez EA, Provenzano E, Ericsson PG, Richardet E, Mehrotra R, Sarancone S, Ehinger A, Rimm DL, Bartlett JMS, Viale G, Denkert C, Hida AI, Sotiriou C, Loibl S, Hewitt SM, Badve S, Symmans WF, Kim RS, Pruneri G, Goel S, Francis PA, Inurrigarro G, Yamaguchi R, Garcia-Rivello H, Horlings H, Afqir S, Salgado R, Adams S, Kok M, Dieci MV, Michiels S, Demaria S, Loi S. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. Npj Breast Cancer 2021, 7: 150. PMID: 34853355, PMCID: PMC8636568, DOI: 10.1038/s41523-021-00346-1.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesImmune checkpoint inhibitorsInternational Immuno-Oncology Biomarker Working GroupBiomarker Working GroupBreast cancerTriple-negative breast cancerSubgroup of womenDeath-1Middle-income countriesPD-L1TIL analysisCytotoxic treatmentCancer settingPrognostic biomarkerClinical utilityClinical validityPatient advocatesWorking GroupClinical utilizationModern oncologyPatientsLymphocytesCancerFuture approachesImmunotherapy
2020
Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, van de Vijver KK, Goel S, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Symmans WF, Sotiriou C, Rimm DL, Hewitt S, Denkert C, Loibl S, Luen SJ, Bartlett JMS, Savas P, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kok M, Horlings HM, Madabhushi A, van der Laak J, Ciompi F, Laenkholm AV, Bellolio E, Gruosso T, Fox SB, Araya JC, Floris G, Hudeček J, Voorwerk L, Beck AH, Kerner J, Larsimont D, Declercq S, Van den Eynden G, Pusztai L, Ehinger A, Yang W, AbdulJabbar K, Yuan Y, Singh R, Hiley C, Bakir MA, Lazar AJ, Naber S, Wienert S, Castillo M, Curigliano G, Dieci MV, André F, Swanton C, Reis-Filho J, Sparano J, Balslev E, Chen IC, Stovgaard EIS, Pogue-Geile K, Blenman KRM, Penault-Llorca F, Schnitt S, Lakhani SR, Vincent-Salomon A, Rojo F, Braybrooke JP, Hanna MG, Soler-Monsó MT, Bethmann D, Castaneda CA, Willard-Gallo K, Sharma A, Lien HC, Fineberg S, Thagaard J, Comerma L, Gonzalez-Ericsson P, Brogi E, Loi S, Saltz J, Klaushen F, Cooper L, Amgad M, Moore DA, Salgado R. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Npj Breast Cancer 2020, 6: 17. PMID: 32411819, PMCID: PMC7217863, DOI: 10.1038/s41523-020-0156-0.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesEarly TNBCBreast cancerHER2-positive breast cancerTumor-infiltrating lymphocytesLymphocyte distributionStromal tumorsInflammatory cellsPredictive biomarkersTreatment selectionPrognostic toolClinical practiceOutcome estimatesLymphocytesReproducible assessmentTNBCTumorsCancerScoring guidelinesMultiple areasTumor boundariesRisk estimationImpact of discrepanciesRing studiesAssessmentReport on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Amgad M, Stovgaard ES, Balslev E, Thagaard J, Chen W, Dudgeon S, Sharma A, Kerner JK, Denkert C, Yuan Y, AbdulJabbar K, Wienert S, Savas P, Voorwerk L, Beck AH, Madabhushi A, Hartman J, Sebastian MM, Horlings HM, Hudeček J, Ciompi F, Moore DA, Singh R, Roblin E, Balancin ML, Mathieu MC, Lennerz JK, Kirtani P, Chen IC, Braybrooke JP, Pruneri G, Demaria S, Adams S, Schnitt SJ, Lakhani SR, Rojo F, Comerma L, Badve SS, Khojasteh M, Symmans WF, Sotiriou C, Gonzalez-Ericsson P, Pogue-Geile KL, Kim RS, Rimm DL, Viale G, Hewitt SM, Bartlett JMS, Penault-Llorca F, Goel S, Lien HC, Loibl S, Kos Z, Loi S, Hanna MG, Michiels S, Kok M, Nielsen TO, Lazar AJ, Bago-Horvath Z, Kooreman LFS, van der Laak JAWM, Saltz J, Gallas BD, Kurkure U, Barnes M, Salgado R, Cooper LAD. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group. Npj Breast Cancer 2020, 6: 16. PMID: 32411818, PMCID: PMC7217824, DOI: 10.1038/s41523-020-0154-2.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesComputer-aided diagnosticsPotential of machineAssessment of algorithmsInternational Immuno-Oncology Biomarker Working GroupHER2-positive breast cancerBiomarker Working GroupComputational workflowPrognostic workflowsVisual guidelinesTIL assessmentInfiltrating lymphocytesBreast cancerPredictive featuresSolid tumorsInter-reader variabilityWorkflowClinical validationComputational assessmentRipe opportunityComputational methodsReporting guidelinesLymphocytesVisual scoringClinical translationApplication of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Hudeček J, Voorwerk L, van Seijen M, Nederlof I, de Maaker M, van den Berg J, van de Vijver KK, Sikorska K, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Michiels S, Symmans WF, Sotiriou C, Rimm DL, Hewitt SM, Denkert C, Loibl S, Loi S, Bartlett JMS, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kos Z, Salgado R, Kok M, Horlings HM. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials. Npj Breast Cancer 2020, 6: 15. PMID: 32436923, PMCID: PMC7217941, DOI: 10.1038/s41523-020-0155-1.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesTriple-negative breast cancerMetastatic triple-negative breast cancerTumor-infiltrating lymphocytesClinical trialsBiomarker-driven clinical trialsPotential predictive biomarkersPotential risk factorsImmunotherapy trialsImmunotherapy responsePredictive biomarkersRisk factorsBreast cancerStratification factorsSpecific trialsIntegral biomarkerTrialsLymphocytesBiomarkersReliable assessmentReviewCancerCompactness measures of tumor infiltrating lymphocytes in lung adenocarcinoma are associated with overall patient survival and immune scores
Ding R, Prasanna P, Corredor G, Lu C, Velu P, Le K, Leo P, Beig N, Velcheti V, Rimm D, Schalper K, Madabhushi A. Compactness measures of tumor infiltrating lymphocytes in lung adenocarcinoma are associated with overall patient survival and immune scores. 2020, 2. DOI: 10.1117/12.2549588.Peer-Reviewed Original Research
2019
MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer
Wang X, Barrera C, Bera K, Lu C, Feldman M, Schalper K, Rimm D, Velcheti V, Madabhushi A. MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s350-s351. DOI: 10.1016/j.jtho.2019.08.710.Peer-Reviewed Original ResearchPhenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer
Barrera C, Corredor G, Wang X, Schalper K, Rimm D, Velcheti V, Madabhushi A, Castro E. Phenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer. Progress In Biomedical Optics And Imaging 2019, 10956: 1095607-1095607-8. DOI: 10.1117/12.2513048.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesTIL densityLung cancerEarly stage non-small cell lung cancer patientsNon-small cell lung cancer patientsCell lung cancer patientsEarly-stage lung cancerKaplan-Meier analysisLung cancer patientsStage lung cancerLikelihood of recurrenceBetter prognosisLate recurrenceCancer patientsDifferent cancer typesDisease outcomeRecurrenceDifferent subtypesCancer typesLymphocytesCancerPatientsPrognosisIndependent validationCorrection: RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. Correction: RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2019, 25: 1437-1437. PMID: 30770496, DOI: 10.1158/1078-0432.ccr-18-4264.Peer-Reviewed Original Research
2018
Prognostic implications of residual disease (RD) tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC).
Luen S, Salgado R, Dieci M, Vingiani A, Curigliano G, Hubbard R, Castaneda Altamirano C, Sanchez J, D'Alfonso T, Cheng E, Castillo Garcia M, Adams S, Ahmed F, Rimm D, Demaria S, Symmans W, Michiels S, Loi S. Prognostic implications of residual disease (RD) tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC). Journal Of Clinical Oncology 2018, 36: 571-571. DOI: 10.1200/jco.2018.36.15_suppl.571.Peer-Reviewed Original Research
2017
Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer
Dieci MV, Radosevic-Robin N, Fineberg S, van den Eynden G, Ternes N, Penault-Llorca F, Pruneri G, D’Alfonso T, Demaria S, Castaneda C, Sanchez J, Badve S, Michiels S, Bossuyt V, Rojo F, Singh B, Nielsen T, Viale G, Kim SR, Hewitt S, Wienert S, Loibl S, Rimm D, Symmans F, Denkert C, Adams S, Loi S, Salgado R, Cancer O. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. Seminars In Cancer Biology 2017, 52: 16-25. PMID: 29024776, DOI: 10.1016/j.semcancer.2017.10.003.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesBreast cancerResidual diseaseTIL assessmentDuctal carcinomaInternational Immuno-Oncology Biomarker Working GroupBiomarker Working GroupClinical breast cancer researchBreast cancer researchNeoadjuvant chemotherapyNeoadjuvant therapyImmunotherapeutic strategiesImmunological biomarkersInvasive carcinomaClinical trialsClinical relevanceConsensus guidanceInternational guidelinesCarcinomaWorking GroupCancerDiseaseMorphological evaluationLymphocytesCancer researchErratum to: Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL. Erratum to: Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 109. PMID: 28946899, PMCID: PMC5613519, DOI: 10.1186/s13058-017-0898-2.Peer-Reviewed Original Research
2014
The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Annals Of Oncology 2014, 26: 259-271. PMID: 25214542, PMCID: PMC6267863, DOI: 10.1093/annonc/mdu450.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesBreast cancerInternational TILs Working Group 2014Human epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Evaluation of hematoxylinFactor receptor 2Immunological biomarkersLymphocytic infiltrationClinical trialsReceptor 2Clinical relevanceClinical validityTumor sectionsPredictive valueTumor tissueStandardized methodologyHistopathological practiceMorphological evaluationLymphocytesCancerCurrent dataFuture studiesVisual assessmentQuantitative assessment of CD3, CD8, and CD20 in tumor-infiltrating lymphocytes and predictive value for response to neoadjuvant chemotherapy in breast cancer.
Brown J, Bai Y, Bossuyt V, Nixon C, Lannin D, Rimm D. Quantitative assessment of CD3, CD8, and CD20 in tumor-infiltrating lymphocytes and predictive value for response to neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2014, 32: 1027-1027. DOI: 10.1200/jco.2014.32.15_suppl.1027.Peer-Reviewed Original Research
1994
Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin
Cepek K, Shaw S, Parker C, Russell G, Morrow J, Rimm D, Brenner M. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 1994, 372: 190-193. PMID: 7969453, DOI: 10.1038/372190a0.Peer-Reviewed Original ResearchConceptsIntraepithelial lymphocytesAdhesion moleculesT cellsIntestinal intra-epithelial lymphocytesEpithelial cellsIntestinal intraepithelial lymphocytesIntra-epithelial lymphocytesMucosal immune systemE-cadherinTissue-specific retentionTissue-specific compartmentalizationLymphoid structuresT lymphocytesImmune systemLymphocyte homingLymphocytesΑEβ7