Abstract 23P
Background
The presence of TILs is a prognostic factor in TNBC. However, the prognostic role of CD4+/CD8+ lymphocytes, as well as the intra- or peritumoral distribution remains controversial. Regarding soluble immune checkpoints, there are still very few studies and their prognostic value is unknown in early TNBC. The aim of this study is evaluate the role of TILs and also the search of non-invasive immune checkpoints markers in early TNBC.
Methods
Prospective observational study was carried out in the University General Hospital of Valencia in 42 early TNBC patients treated with neoadjuvant chemotherapy (NACT). Blood samples were collected before NACT. 17 plasma immune checkpoints were analyzed using a preconfigured panel based on Luminex xMAP®. R program was used for statistical analysis. P-value <0.05 was considered statistically significant.
Results
Mean age: 55 years (28-77). 52.4% stage I/II and 47.6% stage III. All NACT schemes included taxanes; carboplatin was added in 17 patients. Mean TILs expression: 30.7% (1-90). Mean relationship between peri- and intratumoral lymphocytes was 68% vs 32% and mean relationship between CD4/CD8 lymphocytes was 70% vs 30%. Expression of TILs ≥30% was associated with better disease-free survival (DFS) and overall survival (OS) (2.25 times lower risk of death). No prognostic differences were found between location and CD4/CD8 lymphocytes proportion. Larger tumor size was associated with higher levels of sPD-1, sLAG3, sTIM-3 and sBTLA. Node involvement was related to higher levels of PD-L1 and sBTLA. Advanced clinical stage was associated with increased levels of sPD-1, sCTLA-4, sTIM-3, sBTLA, sTLR-2, sICOS, sCD27 and sCD28. Increased levels of sCD86/B7-2 were predictive of a lower response to NACT. High basal levels of sTIM-3 were associated with a lower DFS. No others soluble immune checkpoints were associated with DFS or OS.
Conclusions
TILs are an important prognostic factor in patients with early TNBC, obtaining increased survival in patients with higher levels, regardless of location and lymphocyte subtype. Besides, we observe that in more advanced tumors there are higher plasmatic levels of soluble immune checkpoints, indicating decreased activity of the immune system.
Legal entity responsible for the study
The authors.
Funding
The authors acknowledge grant CB16-12-00350 from CIBERONC, the AMACMA foundation, and Lopez Trigo 2017.
Disclosure
All authors have declared no conflicts of interest.