32P - Immune T cell subsets dynamics in the early TNBC treatment setting

Background

There is an urgent need for biomarkers to tailor neoadjuvant treatment (NAT) in early triple-negative breast cancer (eTNBC). The characterization of circulating immune subsets could provide additional information which, added to other factors, may guide clinical decisions.

Methods

In this non-randomized prospective study, patients (pt) were treated with chemotherapy (docetaxel/carboplatin or sequential paclitaxel/carboplatin with doxorubicin/cyclophosphamide) with or without pembrolizumab. Immune cell subsets were analyzed in blood by multicolor flow cytometry (MFC). Adjusted paired 2-way ANOVA was done to compare immune subsets. In this first analysis, we report the frequencies of T cell subsets before and 21 days after completing NAT, and their relationship with pathological response.

Results

15 pt achieved pathological complete response (pCR) while 6 had a RCB score of II-III. Significant differences emerged between pCR (responders) and RCB (non-responders) after NAT (Table). Non-responders presented higher drops in total lymphocytes and CD4 cells (p > 0.05). All pt increased CD8 cells, being significant only in responders (p = 0.013). CD8 subsets exhibited distinct behavior based on response. After NAT, responders showed lower activated CD8 cells, whereas non-responders had the opposite trend. Post-NAT activated CD8 cells were lower in responders (p = 0.048). An opposing pattern was observed in the dynamics of the naïve and effector memory CD8 cells (p > 0.05). In the CD4 population, after NAT all pt showed decreased activated CD4 cells. These changes were deeper and significant in responders (p = 0.048). There were no significant differences between responders and non-responders in other CD4 subsets. Table: 32P

% of cells after NAT according to response

Conclusions

In this study, there were significant differences in the peripheral T cell subsets based on NAT response, suggesting that there may be a systemic immune activation that could impact disease control. Further research is warranted to validate and amplify these observations.

Legal entity responsible for the study

The authors.

Funding

Instituto de Salud Carlos III (ISCIII) PI22/01346, cofinanciado por la Unión Europea.

Disclosure

I. Echavarria Diaz-Guardamino: Financial Interests, Personal, Advisory Board: Lilly, AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Teva, Novartis, Pfizer, Lilly. Y. Jerez Gilarranz: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Novartis, Roche, Pfizer. F. Moreno Anton: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Daiichi Sankyo, MSD, Gilead; Financial Interests, Institutional, Research Grant: Pfizer. J.î García Saenz: Financial Interests, Personal, Advisory Board: Seagen, Gilead; Financial Interests, Personal, Speaker, Consultant, Advisor: Sanofi, Novartis, Celgene, Lilly, Eisai, AstraZeneca, MSD, Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel: Novartis, Roche, Pfizer. C. Bueno Muiño: Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, GSK, Lilly; Financial Interests, Personal, Advisory Board: Pfizer. T. Massarrah: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Roche, GSK; Financial Interests, Personal, Other, Travel: Novartis, AstraZeneca. M. Martin Jimenez: Financial Interests, Personal, Research Grant: PUMA; Financial Interests, Personal, Advisory Board: Lilly, Sanofi, Novartis, Seagen, Roche, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche, Seagen, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Leadership Role: GEICAM, TRIO. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Roche, Pfizer, Veracyte, Pierre Fabre, Lilly, Seagen, Daiichi Sankyo, Europe GmbH, Gilead Sciences, MSD, GSK. All other authors have declared no conflicts of interest.