1948P - Analysis of cytokines, chemokines, and tumor-infiltrating lymphocytes as immunological markers predicting pathological complete response in triple-negative breast cancer: Exploratory analysis of the NACATRINE trial

Background

The search for immunological markers capable of predicting pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) has been an area of intense research. In this study, we explored the analysis of cytokines, chemokines, and tumor-infiltrating lymphocytes (TILs) as potential immunological markers predictive of pCR in patients with TNBC using data from the NACATRINE clinical trial.

Methods

We assessed the expression of immune-related genes in untreated TNBC samples to correlate with neoadjuvant chemotherapy (NAC) outcome. RNA was extracted from biopsy tissue, and the analysis of cytokines and chemokines was conducted using the nCounter® Breast Cancer™ panel. Tumor-infiltrating lymphocytes (TILs) were assessed as a continuous parameter and categorized into two predefined groups: low (sTILs: 0–10%), and high (sTILs: ≥60%).

Results

The results revealed that cytokines and chemokines such as CCL5, CXCR6, and CXCL9, and immune-related markers GZMH and GZMA were significantly overexpressed in association with pCR. When combined, these markers and cytokines/chemokines together with TILs exhibited an area under the curve (AUC) of 0.82. The odds ratio univariate for the genes was combined with weighted linear regression analysis revealed an OR of 11.54. Notably, when stratified by elevated TILs, all cytokines had OR values above 11.54, ranging from 12.00 to 40.92. On the other hand, when stratified by low TILs, only CXCL9 presented an OR of 12.00, while the others ranged from 2.17 to 8.40. These findings suggest a strong association between the expression of these markers and pCR, especially in cases with elevated levels of TILs.

Conclusions

The study highlights the potential of specific cytokines and chemokines, in conjunction with TILs, as predictive biomarkers for pCR in patients with TNBC undergoing NAC. Further validation of these results is needed to elucidate their clinical relevance and potential for personalized therapeutic interventions in TNBC.

Clinical trial identification

NCT02978495.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

DECIT.

Disclosure

All authors have declared no conflicts of interest.