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
3117 - A modified Edmonton Symptom Assessment Scale for assessing symptoms in one day chemotherapy clinic
Presenter: Anjuleta Kampitsi
Session: Poster Display session 3
Resources:
Abstract
6058 - Level of physical activity and nutritional status in cancer patients with fatigue: an exploratory cross-sectional study
Presenter: Patrick Jahn
Session: Poster Display session 3
Resources:
Abstract
1980 - Catheter related necrotizing fascitiis in haematological patients. Case report and implications for nursing
Presenter: Arianna Rosich Soteras
Session: Poster Display session 3
Resources:
Abstract
3984 - Everyday life with Long-term Chemotherapy Induced Peripheral Neuropathy among Patient in Adjuvant Treatment for Colorectal Cancer – a Multi Methods Study
Presenter: Marlene Jensen
Session: Poster Display session 3
Resources:
Abstract
2202 - Scalp cooler is effective in reducing chemotherapy-induced alopecia among breast cancer patients : a single institution experience
Presenter: Emilia Gianotti
Session: Poster Display session 3
Resources:
Abstract
5942 - Nursing management of fatigue in cancer patients: mixed methods study
Presenter: Angela Tolotti
Session: Poster Display session 3
Resources:
Abstract
2930 - Awareness of Nursing Students about the Warning Signs of Cancer
Presenter: Hatice Yakar
Session: Poster Display session 3
Resources:
Abstract
2978 - Assessment of quality of life in patients with cancer and diabetes 2 in Northern Greece.
Presenter: STYLIANI MICHALOPOULOU
Session: Poster Display session 3
Resources:
Abstract
3400 - Radiation dose variables related to the causes of skin toxicities in women with breast cancer: a study proposal
Presenter: EULALIA PUJOL
Session: Poster Display session 3
Resources:
Abstract
2156 - How should the symptoms be managed after breast cancer surgery? An example of mobile app
Presenter: AYDANUR AYDIN
Session: Poster Display session 3
Resources:
Abstract