Increased Stromal Lymphocytes In Breast Cancer Patients With Autologous Dendritic Cell Vaccination Plus Neoadjuvant Chemotherapy

I Baraibar, P Martin-Romano,Luis Mejías,B Perez Solans,Lucia Ceniceros, J Legazpi,I Gardeazabal,S Inoges, A Lopez-diaz,Miguel Angel Idoate, A Cordoba,Marta Santisteban

CANCER RESEARCH(2017)

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摘要
Abstract Introduction: Higher levels of TILs after neoadjuvant chemotherapy (NAC) in the residual tumor have been related to a better outcome in BC patients. According to International TILs working group (2014), we have quantified stromal TILs in a cohort of patients treated with NAC plus dendritic cell vaccines (cohort V) (NCT01431196 plus an expanded cohort) and in an historic cohort of patients treated with the same NAC without V (cohort C) in order to assess if the addition autologous dendritic cell vaccination pulsed with patient´s tumor lysates helps to increase TILs in the residual BC specimen. Our previous data with these cohorts of patients have shown an improved pCR and the stimulation of lymphocytes population in the peripheral blood from cohort V. Methods: Classification of molecular subtypes was performed by IHC. We evaluated percentage of TILs by three different pathologists using stained HE core biopsy sections in paired samples taken at diagnosis (preNAC) and after surgery (postNAC) in a prospectively defined retrospective analysis. Results: 79 patients were evaluated (cohort C 42; cohort V 37). Patients from V cohort were younger (p=0.01). Cohorts were well balanced for AJCC staging, molecular subtypes (cohort C: LA 26%, LB 45%, TN 29%; cohort V: LA 24%, LB 40%, TN 35%), stromal TILs preNAC [cohort C: median 9 (range, 1-24); cohort V: 6 (1-34); p=0.38] and stromal TILs postNAC [cohort C: 9 (2-52); cohort V 8 (4-50); p=0. 94]. Seventy-seven patients (97%) underwent surgery (cohort C 41; cohort V 36). Pathologic CR was higher in Cohort V (27% vs 7%; p=0.02). However a superior pCR rate was detected in TNBC subtype (cohort C 27%; cohort V 58%; p=0.15). Patients from Cohort V experienced an increment of stromal TILs after NAC plus autologous dendritic cell vaccination (preNAC: 6 (1-34); postNAC 8 (4-50); p=0.03), especially in TNBC [preNAC 14 (1-34); postNAC 30 (10-50); p=0.2]. A correlation analysis by Pearson´s R coefficient stated a strong association in V cohort between stromal TILs preNAC and postNAC (R=0.83) as well as a moderate correlation between stromal TILs postNAC and and molecular subtypes (R=0.6). Table 1. Differences in Stromal TILs between studied cohorts PreNAC (median, range)PostNAC (median, range)P valueCohort C9 (1-66)9 (2-52)0.22Cohort V6 (1-34)8 (4-50)0.03*Cohort C LA LB TN5 (1-10) 9 (1-24) 12 (10-24)6 (3-12) 10 (2-40) 13 (5-52)0.69 0.17 1Cohort V LA LB TN5 (2-17) 6 (1-15) 14 (1-347 (4-12) 7 (4-27) 30 (10-50)0.18 0.08 0.2 Conclusion: Pathological complete responses were higher in BC patients treated with neoadjuvant chemotherapy plus active immunotherapy. The addition of autologous dendritic cell vaccines to NAC increases significantly stromal TILs in breast cancer patients. Citation Format: Baraibar I, Martin-Romano P, Mejías L, Perez Solans B, Ceniceros L, Legazpi J, Gardeazabal I, Inoges S, Lopez-diaz A, Idoate M, Cordoba A, Santisteban M. Increased stromal lymphocytes in breast cancer patients with autologous dendritic cell vaccination plus neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-01.
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autologous dendritic cell vaccination,dendritic cell,breast cancer patients,breast cancer
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