Abstract P2-04-09: The prognostic and predictive effect of tumor infiltrating lymphocytes is not determined by B-cells or PD-L1 expression in inflammatory breast cancer
Authors: Van Berckelaer C , Parizel M , Van Dam P , Dirix L , Rypens C , Bertucci F , Schats KA , Kockx MM , Van Laere S , Colpaert C 
Published: May 2019

Abstract
Background
The tumor stroma with tumor infiltrating lymphocytes (TILs) plays a crucial role in the aggressive inflammatory breast cancer (IBC) phenotype and a gene signature enriched for immunity-related genes showed that response to neo-adjuvant chemotherapy was associated with immunity related processes in IBC. In both IBC and non-inflammatory breast cancer (nIBC), tumors are infiltrated by B-cells, but their role in regulating anti-tumor immunity is not well understood. In this study we looked at the prognostic and predictive effect of B-cells in the immune infiltrate of 178 IBC and 247 nIBC patients.
Methods
TIL scoring was done on standard H&E stained sections of formalin-fixed paraffin-embedded pre-treatment tumor tissue according to international guidelines (Salgado et al., 2015). B-cells in the immune infiltrate were defined as CD79α (clone JCB117) positive cells and scoring was done semi-quantitatively, both intra- and peritumorally. Slides, stained with a validated PD-L1 assay (clone SP142) were scored on immune cells (IC) according to Herbst et al., 2014.
Results
Most of our IBC patients presented with a grade 3 (67.7%), ductal (91.1%) carcinoma. A quarter of the patients (25.7%) with initially localized disease (71.6%) achieved complete pathological response (pCR) after neo-adjuvant chemotherapy.The mean TIL score was 18.02% (1.0 – 80.0) and 67 out of 156 patients (42,9%) were PD-L1 positive. Categorical scores of the immune infiltrate are summarized in the table.
Category 1 (&lt; 10%)Category 2 (≥ 10, &lt; 40%)Category 3 (≥ 40 %)TIL score (n=178)34.73% (n= 61)53.4% (n= 95)12.4% (n=22)Intratumoral CD79α score (n= 175)69.1% (n= 121)22.3% (n= 175)8.6 % (n= 15)Peritumoral CD79α score (n= 171)48.5 % (n= 83)38.0 % (n= 65)13.5 % (n= 23)
TILs were significantly higher in oestrogen receptor negative (ER-) groups compared to ER+ groups (21.26% vs. 15.58%, p= 0.017). In IBC, univariate analysis showed that achieving pCR was significantly associated with more TIL infiltration (p&lt; 0.001), PD-L1 IC expression (p= 0.013) and intratumoral CD79α scores (p= 0.036). However, in multivariate analysis the effect of PD-L1 and CD79α positive cells was lost. When corrected for different molecular subtypes the predictive effect of TILs was only present in ER- groups. Survival analysis showed a significant beneficial effect of TILs (p= 0.014) but only in the ER+ groups, while PD-L1, intra- and peritumoral CD79α scores were not significant. Intratumoral CD79α scores correlated with both TIL score (p= 0.024) and PD-L1 expression (p= 0.007) in multivariate analysis.
When comparing IBC to nIBC, TILs were significantly higher in IBC patients (15.58 % vs. 11.29%, p= 0.009) in the ER+ group, while in the ER- group they were significantly lower (21.27% vs. 37.19%, p &lt; 0.001). This was also seen for CD79α peritumoral positivity, but logistic regression revealed that this was a TILs effect.
Conclusion
A high TIL score correlates with a better OS and pCR in IBC, depending on the ER status. B-cells and PD-L1 expressing IC appear not to contribute to this effect, but do correlate independently with each other. Further research is needed to unravel the driving and targetable components of the immune responses in IBC.
Citation Format: Van Berckelaer C, Parizel M, Van Dam P, Dirix L, Rypens C, Bertucci F, Schats KA, Kockx MM, Van Laere S, Colpaert C. The prognostic and predictive effect of tumor infiltrating lymphocytes is not determined by B-cells or PD-L1 expression in inflammatory breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-09.