TNBC is an aggressive breast cancer subtype that needs further molecular characterization to develop targeted therapy to improve its outcome. The ability of BCSCs to evade the immune system is one of the resistance mechanisms to chemotherapy, that remains the standard treatment. Neoadjuvant chemotherapy (NACT) could induce changes in the BCSCs subpopulation and the patients' immune response. New therapeutic strategies based on blocking this subpopulation are being evaluated.
In a retrospective study, we included 25 early TNBC patients resistant to NACT diagnosed in the Catalan Institute of Oncology (Girona, Spain) between 2010-2019. We collected 50 paired samples (pre and post NACT) from the Tumor Biobank. We determined BCSCs biomarkers (CD44+, CD24- and ALDH1) and PD-L1 by immunohistochemistry (IHQ) and TILS expression by hematoxylin-eosin stain. Clinicopathological characteristics from all patients were collected.
Mean age was 51 years old, almost 80% of tumors were ductal invasive carcinomas, 76% were grade 3 with a mean Ki-67 of 57.46%, 83% were cT2-3, 62% were node positive at baseline, 86% of patients received anthracyclines/taxanes and, at the time of data cut-off, 52% were alive, with a median follow-up of 43 months. At baseline, 46% of the tumors showed CD44 high expression, 52% showed CD24 low expression, 4% showed ALDH1 high expression, 79% were PD-L1 ≤ 1% (negative) and 60% had low expression of TILS. A statistically significant association was found between PD-L1 expression and NACT, since 52% of PD-L1-negative tumors became PD-L1 positive (> 1%) after NACT (p=0.002). No changes in BCSCs markers (CD44, CD24, ALDH1) and TILS expression were found. No association was found between high baseline BCSCs enriched subpopulation and PD-L1 changing expression after NACT.
Understanding therapeutic resistance is a major challenge in TNBC. We have observed that TNBC chemotherapy resistant tumors increase PD-L1 expression after neoadjuvant therapy. More studies are needed to evaluate the relationship between BCSCs and immunogenicity profile to develop new co-therapeutic strategies.
The authors.
Oncoswim - Fundació Oncolliga Girona.
All authors have declared no conflicts of interest.