Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.

Abstract

519 Background: Higher baseline TILs and PD-L1 expression are associated with greater pathologic complete response (pCR) rates, but how chemotherapy affects these immune parameters is unknown. The goal of this study was to examine TIL and PD-L1 expression in pre- and post-NAC tumor specimens from the S0800 clinical trial that compared weekly nab-paclitaxel/bevacizumab + dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel + AC as NAC for HER2-negative cases. Association between immune parameters, pCR and NAC-induced changes were tested using ER and NAC-arm adjusted logistic regression. Methods: TILs were assessed on H&E stained full sections of 120 pre- and 62 post-NAC tissues (tumor bed of pCR) including 59 matched samples. PD-L1 immunohistochemistry was performed using the FDA cleared 22C3 assay and results were available for 121 baseline and 43 matched post-NAC samples. Results: At baseline, the mean TIL count was 18%; 16% had no TILs and 9% had > 50% TILs. Higher baseline TILs were associated with higher pCR rate (p = 0.043, trend test p = 0.014) but there was no interaction with NAC arm. Post-NAC, the mean TIL counts was 11%; 5% had no TILs and 1.6% had > 50% TILs. In the matching post-NAC samples, the mean change was 15% decrease in TILs, but in 32% of cases TILs increased. Cases with residual disease (n=44) had lesser average decrease (p=0.029) than cases with pCR (n=15). The post-NAC decrease in TILs was also observed after excluding cases with pCR. At baseline, PD-L1 expression either in the stroma or on epithelial cells or in both was detected in 52 (43%) of 121 cases (5 tumor only, 29 stroma only, 18 tumor + stroma). Those with baseline PD-L1 expression had higher pCR (63% vs. 37%; p=0.008). Post-NAC, PD-L1 expression was seen in 14 of 43 (33%) cases (7 stroma only, 7 tumor + stroma). In the 39 matching pre- and post-NAC samples, PD-L1 expression was negative in both in 20, positive in both in 10 cases and 6 patients had PD-L1 expression at baseline but not in the post-NAC sample. Conclusions: TIL counts and PD-L1 expression generallydecreased, but in a minority of cases increased after NAC. The decrease in TIL was significantly greater in cases achieving pCR. Clinical trial information: NCT00856492.