Abstract 2316
Background
Neoadjuvant chemotherapy (NACT) is the treatment option for locally advanced breast cancer (BC). However, more than half of the patients have no response. Thus, there is an urgent need to find biomarkers of NACT response and personalized therapies for non-responders. Recently, we described a biomarker of NACT response, assessed both in biopsy and blood - HLA-DR expressing cytotoxic T cells (CTLs) with a sensitivity and specificity of 94.12% and 100%, respectively. HLA-DR is associated with CTLs’ cytotoxicity, and it was only observed in NACT-responders, suggesting that functional CTLs are required in the tumor for NACT success. Now, we are validating these results in an independent cohort. Simultaneously, we are establishing 3D spheroid co-culture platforms to tackle new therapeutic options for NACT non-responders.
Methods
MCF7 BC cell line was used to spontaneously form a spheroid in agarose coated plates. Peripheral blood mononuclear cells (PBMCs) from NACT-responders or non-responders were added after spheroid formation and they were able to infiltrate the structure. Doxorubicin (doxo), anti-PD-1 and anti-PD-L1 were added in different combinations.
Results
The validation of HLA-DR level in CTLs to predict NACT response has been in agreement with the first cohort. Regarding the BC spheroids, doxo alone or in combination with NACT non-responders PBMCs (low HLA-DR in CTLs) did not affect them. However, when PBMCs from NACT responders (high HLA-DR in CTLs) were added in combination with doxo, the viability and proliferation of MCF7 cells reduced significantly. Notably, when PBMCs from NACT non-responders were stimulated ex vivo, to increase CTLs’ HLA-DR level and IFN-γ production (p = 0.002), MCF7 cells viability decreased (p = 0.0007). Considering that in biopsies of non-responders, the low HLA-DR level in CTLs was negatively correlated with the expression of tumor PD-L1, we are also exploring this platform to inhibit the PD-1/PD-L1 axis in order to stimulate the PBMCs and decrease BC cells viability.
Conclusions
Besides determining if BC patients will respond to NACT, by analysing HLA-DR levels in CTLs, we will now be able to define the best therapy to NACT non-responders, hopefully improving the BC treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Fundação para a Ciência e Tecnologia (FCT) - PD/BD/114023/2015 and PTDC/BBB-BMD/4497/2014. Liga Portuguesa Contra o Cancro - LPCC-NRS/Terry Fox 2019/2020.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract