Abstract 150P
Background
Checkpoint proteins regulate the immune system. Breast cancer (BC) cells can up-regulate or down-regulate these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICMs) can be measured in human plasma. The study aimed to measure the systemic levels of a series of positive and negative ICMs at diagnosis, post-neo-adjuvant chemotherapy (NAC) and post-surgery in newly- diagnosed BC patients (pts) relative to those of a healthy control group.
Methods
Soluble ICMs were measured using Multiplex® bead array technology in plasma from 72 BC pts and 45 healthy controls. Data was prospectively obtained, and levels compared between pre-treatment, post-NAC, and post-surgery using non-parametric tests.
Results
Pre-treatment, soluble stimulatory molecules viz. GITR (p<0.0000), GITRL (p< 0.0199), CD27 (p< 0.0243), CD40 (p< 0.0209), ICOS (p< 0.0087), as well as the inhibitory molecules PD-L1 (p< 0.0000), CTLA-4 (p< 0.005), TIM-3 (p< 0.0004), HVEM (p< 0.0004) levels were significantly lower in early BC pts compared to controls. Post treatment, there were significant increases in most ICM levels (Table), with the exception of CTLA-4 which decreased significantly following treatment. A pCR was documented in 65% of patients (mostly TNBC). No correlation between pre-treatment ICM levels and pCR. Table: 150P
| ICM | Control | Diagnosis (Group A) | Post-NAC (Group B) | Post-surgery (Group C) | Group A vs Group B Comparing pre-treatment levels vs post-treatment levels |
| Median (pg/ml) | p-value | ||||
| BTLA | 18147 | 13022 | 9987 | 12777 | 0,0366 |
| CD80 | 2329 | 1678 | 3048 | 3611 | 0,0000 |
| CD86 | 14297 | 11585 | 9922 | 12439 | 0,2789 |
| CTLA-4 | 2618 | 1566 | 598 | 687 | 0,0000 |
| LAG3 | 150416 | 131275 | 464880 | 500133 | 0,0000 |
| PD-L1 | 3342 | 1647 | 4794 | 5215 | 0,0000 |
| PD-1 | 14917 | 12305 | 13350 | 15076 | 0,8888 |
| TIM3 | 5047 | 3897 | 9975 | 9615 | 0,0000 |
| CD27 | 4577 | 3342 | 5351 | 5427 | 0,0000 |
| CD28 | 46135 | 32914 | 44277 | 50058 | 0,0415 |
| CD40 | 1977 | 1523 | 2030 | 2054 | 0,0002 |
| GITR | 3797 | 1497 | 4035 | 4434 | 0,0000 |
| GITRL | 7151 | 5886 | 5339 | 5927 | 0,4938 |
| ICOS | 26506 | 15123 | 26586 | 29746 | 0,0001 |
| HVEM | 2290 | 1865 | 4047 | 3950 | 0,0000 |
| TLR2 | 30477 | 26831 | 33837 | 37042 | 0,0257 |
Conclusions
We identified low levels of stimulatory and inhibitory ICMs in newly-diagnosed, non-metastatic BC patients compared to healthy controls. Post treatment, (except CTLA-4) most of these pre-treatment abnormalities of systemic ICM levels corrected. NAC is associated with upregulation of sPD-L1 and most other ICMs. These results indicate that early BC is associated with down-regulation of soluble stimulatory and inhibitory ICMs. Newly-diagnosed early BC patients appear to have generalized immune-suppression independent of subtype and stage. To our knowledge, this is the first study to describe the effect of treatment on systemic ICMs in early BC pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CANSA.
Disclosure
All authors have declared no conflicts of interest.