Abstract 114P
Background
Chemotherapy (CT) influences lymphocyte count; we planned this observational prospective trial to describe regulatory (TREG) and effectors T lymphocyte (TEFF) subsets whose balance can be involved in tumor progression, focusing on TEFF/TREG rate kinetic across adjuvant CT in early breast cancer patients.
Methods
We enrolled 10 patients undergoing CT (doxorubicin + paclitaxel (AT) x 3 → 3 cycles of CMF 1-8 +/- trastuzumab based on HER2 status). All patients were HR+, 3 were HER2+. In compliance with the International TILsWorking Group, we used antibodies (Ab) directed to CD3, CD4, CD8, CD68, CD163, CD56, FOXP3; we also tested PD-L1, NY-ESO1. Time-points for blood samples were baseline, day 10 of each AT cycle and day 1, 14 and 21 of each CMF cycle. T, B, NK lymphocyte subsets and monocytes were evaluated by flow cytometry (BD FACSCanto II) with appropriate Ab. Absolute leukocyte subsets counts and relative values versus baseline were obtained. The kinetic of TREG (CD39+ and CD39-) and TEFF (CD8+CD45RA+/CCR7-/CD27-/CD28-) was also defined. We studied the influence of three variables on lymphocytes subsets: CT regimen, cycle number and day of treatment, using an ANOVA analysis for repeated measures using the PROC MIXED procedure, and a statistically significant a conventional p–value of ≤0.05 for a 2-sided test.
Results
PD-L1 stained negative in all cases but one; all tumors were NYESO1 negative. TILs percentage was higher than 5% in all samples. All variables affected B lymphocytes. CT regimen and day of treatment affected most lymphocyte subsets, including TEFF and TREG; a significant increase of TEFF (p<0.0001) was detected during AT regimen, followed by a reduction during CMF; conversely, TREG increase was significant during CMF (p=0.0005) in all patients, especially for the CD39+ subset. The TEFF/TREG rate was considerably higher during AT vs CMF. Focusing on TEFF/CD39+ TREG rate, we observed a spike just after the first cycle of AT (CT regimen-cycle interaction p=0.03).
Conclusions
CT influences lymphocytes subsets regardless of the presence of tumor; TEFF/TREG rate kinetic across adjuvant CT could guide timing of cancer vaccines/immunotherapy administered in combination.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Cresta: Non-Financial Interests, Institutional, Principal Investigator: Taiho Oncology, Inc, Phost’In Therapeutics SAS. S. Damian: Non-Financial Interests, Institutional, Principal Investigator, serving as a principal investigator for Roche, Incyte, Nerviano Medical Science, Pfizer: Incyte; Non-Financial Interests, Institutional, Principal Investigator: Roche, NMS, Pfizer. M. Duca: Non-Financial Interests, Personal, Principal Investigator, serving as a principal investigator for Bayer: Bayer. G. Mariani: Non-Financial Interests, Institutional, Principal Investigator: Fondazione Michelangelo. R. Lobefaro: Non-Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Accord; Non-Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other: Eli Lilly. C. Vernieri: Non-Financial Interests, Personal, Advisory Board: Novartis, Lilly, Pfizer; Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Istituto Gentili, Accademia di Medicina; Financial Interests, Institutional, Research Grant: Roche. M. Di Nicola: Non-Financial Interests, Institutional, Principal Investigator: Novartis, BMS, Genentechh, BeiGene, Incyte. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Amgen, Ambrosetti, Ambrosetti, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Accmed, Dynamicom Education, BMS, Basilea Pharmaceutica International AG, Daichii Sankio Dev. Limited, Exelixis Inc, F. Hoffmann-LaRoche Ltd., IQVIA, Ignyta Operating INC, Janssen-Cilag International NV, Kymab, Loxo Oncology Incorporated, MSD, MedImmune LCC, Merck KGAA, Merck Sharp & Dohme Spa, Novartis, Pfizer, Tesaro; Financial Interests, Personal, Other, Think Thank: MCCann Health; Financial Interests, Personal, Other, Consultant: Mattioli 1885; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other, Consultant Advisory Board: AstraZeneca, BMS, EMD Serono, Incyte, MSD, Menarini, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other, Consultant Adv Board: Taiho. All other authors have declared no conflicts of interest.