Abstract 1946P
Background
Checkpoint proteins regulate the immune system. Breast cancer (BC) cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICM) can be measured in human plasma, however their biological and clinical significance remains essentially unknown. The aim of the present analysis was to measure the levels of pre-treatment ICM in newly diagnosed BC patients (pts) and compare them to healthy controls.
Methods
Soluble forms of ICM, as well as cytokines and chemokines, were measured using Multiplex® bead array and ELISA technologies. Plasma samples from 98 BC pts and 45 healthy controls were analyzed for each protein. Data was prospectively obtained. Measured levels were compared between BC pts and healthy controls using a non-parametric test (Mann-Whitney).
Results
Soluble stimulatory molecules GITR (p<0.000002), GITRL (p< 0.007), CD27 (p< 0.002), CD28 (p<0.003), CD40 (p< 0.003), CD80 (p< 0.009), ICOS (p< 0.0006), as well as inhibitory molecules PD-L1 (p< 0.0000001), CTLA-4 (p< 0.005), TIM-3 (p< 0.00006), HVEM (p< 0.00002) TLR-2 (p< 0.05), levels were significantly lower in early BC pts compared to healthy controls. When analyzed according to BC characteristics (TNBC vs. non-TNBC, tumor size, stage, nodal status and age) no significant difference was detected between the soluble levels of these ICM between the different subsets. Additionally, serum levels of CXCL5 (p< 0.000001), CCL23 (p< 0.04), IL-16 (p< 0.00005), interferon-α (p< 0.03) and IL1-RA (p< 0.03) were significantly lower compared to healthy controls. Serum CX3CL1 or fractalkine (p< 0.024465) was significantly higher compared with healthy controls.
Conclusions
We identified low levels of both the stimulatory and inhibitory ICM in newly diagnosed, non-metastatic BC pts compared to healthy controls. These results indicate that early BC is associated with a down-regulation of both soluble stimulatory and inhibitory immune-checkpoint pathways. Newly diagnosed early BC pts have a generalized immune-suppression independent of subtype and stage, which, to our knowledge, is the first study to describe soluble immune checkpoints in early BC pts.
Clinical trial identification
BB1.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CANSA (Cancer Association of South Africa), South African NRF (National Research Foundation).
Disclosure
All authors have declared no conflicts of interest.