Abstract 1815P
Background
Conventional type 1 dendritic cells (cDC1) are more efficient than other DCs subpopulations in cross-presenting cellular antigens. We previously shown by in silico analysis that cDC1 were the most strongly associated with a prolonged overall survival (OS) in the majority of solid tumours including breast cancer. However, their prognostic value and their precise localization has never been validated by in situ approach due to the lack of specific antibodies. Here, we describe cDC1 infiltration in Ductal Carcinoma In situ (DCIS) and in invasive triple negative breast cancer (TNBC). Then, we analyse their prognostic value in TNBC.
Methods
A cohort of 15 DCIS and 77 TNBC patients was collected. We set up an RNA in situ hybridization allowing cDC1 (anti-CLEC9A) identification along with CD8. DCIS patients were categorized as cDC1+/- and CD8+/-. TNBC were classified as cDC1-high/low and CD8-high/low according to the mean number of cDC1 and CD8. Mann-Whitney test was used for all mean comparisons except for the lymph nodes status (Krusal-Wallis). Survival curves were obtained using the Kaplan–Meier method.
Results
Seven (43%) DCIS patients were cDC1+/CD8+, seven (43%) were cDC1-/CD8- and 1 patient (8%) was cDC1+/CD8-. In contrast to DCIS, cDC1 were detected in all TNBC analysed. In TNBC, the mean cDC1 and CD8 density was 11 and 292 cell/mm2 respectively. A higher cDC1 density was found when tumours were grade III, did not have vascular embolism and did not relapse with a median follow-up of 7 years. A higher CD8 density was found when tumour was grade III. The lack of vascular embolism (disease free survival [DFS]: p = 0.001, OS: p <0.0001), having less than 3 lymph nodes involved (DFS: p < 0.0001, OS: p < 0.0001), being classified as CD8-high (DFS: p = 0.015, OS: p = 0.047) and cDC1-high (DFS: p = 0.002, OS: p=0.004) were found associated with a longer 5-year DFS and OS. Moreover, patients being cDC1-high had a better DFS regardless of CD8 infiltration, compared to cDC1-low ones (p = 0.026).
Conclusions
cDC1 was found in DCIS suggesting a role for this DC subset in immunosurveillance. cDC1 infiltration in TNBC is a good prognostic factor regardless of the CD8 infiltration which confirms our previous in silico observations and identify cDC1 as potential target for future treatments.
Clinical trial identification
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Editorial acknowledgement
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Legal entity responsible for the study
The authors.
Funding
ESMO translational fellowship, INSERM, CNRS, UCBL, CLB, ANR, INCA, Région Auvergne-Rhône Alpes, Ligue Contre le Cancer.
Disclosure
All authors have declared no conflicts of interest.