Impact of CD8 stromal lymphocytes in BC patients with the addition of autologous dendritic CELL vaccination to neoadjuvant chemotherapy.
ABSTRACT
Background: Levels of tumor infiltrating lymphocytes (TILs) at diagnosis have shown to improve survival in TNBC and HER2 overexpressing breast cancer (BC) patients. Indeed, high levels of TILs after neoadjuvant chemotherapy (NAC) in the residual tumor have been related to a better outcome in BC patients. Thus, we have quantified stromal CD8 TILs pre- and postNAC in our cohort of patients treated with NAC plus dendritic cell vaccines (cohort V) (NCT01431196) and in an historic cohort of patients treated with the same NAC without the vaccine (cohort C) in order to check if the addition of immunotherapy helps to increase TILs in the residual BC. Our previous data have showed an improved pCR and the stimulation of lymphocyte populations in the blood in cohort V.
Methods: Classification of molecular subtypes was performed based on IHC. We evaluated percentage of TILs by two different pathologists using stained CD8 core biopsy sections taken at diagnosis and after NAC therapy in a prospectively defined retrospective analysis.
Results: TNBC patients achieved a pCR of 17% vs 67% in the C and V groups. Thirty patients who did not reach pCR to NAC in the C cohort and 24 in the V cohort were included. Age, molecular subtypes, Ki67 and TNM stage were well balanced between cohorts. According to stromal TIL quantification, no statistical differences were found at diagnosis (median 5% (1, 40) for both C and V; p = 0.76) and after treatment (5% (1, 50) and 2% (1, 50); p = 0.22) nor in the C and V cohorts. Levels of stromal TILs in paired samples (pre- and postNAC) were not significant in the C (p = 0.69) and the V cohorts (p = 0.09). However, stratifying to molecular subtypes, TNBC patients showed increased TILs after vaccine (37.5% vs. 42.5%; p = 0.01). A correlation analysis stated a strong association between stromal postNAC CD8 TILs and IHC subtypes (R = 0.71). A moderate association between postNAC stromal CD8 TILs and Ki67% (R = 0.45) was shown.
Conclusions: pCR were higher in TNBC patients treated with NAC who received the vaccines. The addition of dendritic cell vaccines to NAC increases significantly stromal CD8 TILs in TNBC patients who did not reach pCR and this fact could improve patient’s outcome.