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. 2018 Jun;17(6):1324-1331.
doi: 10.1158/1535-7163.MCT-17-1005. Epub 2018 Mar 27.

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial

Vasiliki Pelekanou  1 , William E Barlow  2 , Zeina A Nahleh  3 , Brad Wasserman  1 , Ying-Chun Lo  1 , Marie-Kristin von Wahlde  4 , Daniel Hayes  5 , Gabriel N Hortobagyi  6 , Julie Gralow  7 , Debu Tripathy  6 , Peggy Porter  7 , Borbala Szekely  4 , Christos Hatzis  4 , David L Rimm  1 , Lajos Pusztai  8
Affiliations

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial

Vasiliki Pelekanou et al. Mol Cancer Ther. 2018 Jun.

Abstract

Our aim was to examine the association of pretreatment tumor-infiltrating lymphocyte (TIL) count and PD-L1 levels with pathologic complete response (pCR) and assess immune marker changes following treatment in tumor specimens from the S0800 clinical trial, which randomized patients to bevacizumab + nab-paclitaxel, followed by doxorubicin/cyclophosphamide (AC) versus two control arms without bevacizumab (varying sequence of AC and nab-paclitaxel). TILs were assessed in 124 pre- and 62 posttreatment tissues (including 59 pairs). PD-L1 was assessed in 120 pre- and 43 posttreatment tissues (including 39 pairs) using the 22C3 antibody. Baseline and treatment-induced immune changes were correlated with pCR and survival using estrogen receptor (ER) and treatment-adjusted logistic and Cox regressions, respectively. At baseline, the mean TIL count was 17.4% (17% had zero TILs, 9% had ≥50% TILs). Posttreatment, mean TIL count decreased to 11% (5% had no TILs, 2% had >50% TILs). In paired samples, the mean TIL change was 15% decrease. Baseline PD-L1 was detected in 43% of cases (n = 5 in tumor cells, n = 29 stroma, n = 18 tumor + stroma). Posttreatment, PD-L1 expression was not significantly lower (33%). Higher baseline TIL count and PD-L1 positivity rate were associated with higher pCR rate even after adjustment for treatment and ER status (P = 0.018). There was no association between TIL counts, PD-L1 expression, and survival due to few events. In conclusion, TIL counts, but not PD-L1 expression, decreased significantly after treatment. Continued PD-L1 expression in some residual cancers raises the possibility that adjuvant immune checkpoint inhibitor therapy could improve survival in this patient population. Mol Cancer Ther; 17(6); 1324-31. ©2018 AACR.

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Conflict of interest statement

Disclosure of Potential Conflict of Interest: All other authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1
CONSORT diagram of samples used in the study.
Figure 2
Figure 2. Tumor infiltrating lymphocyte (TIL) counts in baseline tumors and residual disease
A. Distribution of TIL percentage counts before and after neoadjuvant chemotherapy. B. Change in TIL count before and after neoadjuvant chemotherapy in paired samples grouped by pathologic response category (pCR=pathologic complete response, n=15; no-pCR n=44). The mean change was 11% in cases with no-pCR and 26% in cases with pCR (Wilcoxon test p=0.04).
Figure 3
Figure 3. Representative images of tumor infiltrating lymphocytes (TIL) and PD-L1 chromogenic staining
A. Baseline H&E of a case with high TIL count (40× magnification, bar represents 100μm). B. Post-treatment H&E of the same case with decrease of the TIL infiltrate. C. In this case, the PD-L1 immunostaining is mostly observed in cells morphologically compatible with macrophages or fibroblasts. D. Example of PD-L1 immunostaining that is not in lymphocytes in a tumor with high lymphocytic infiltration, staining is localized to cells that are morphologically compatible with macrophages. E. A case with baseline high PD-L1 expression in tumor cells. F. Example of a PD-L1 negative case.
Figure 4
Figure 4. PD-L1 expression at baseline and in residual disease of paired samples
PD-L1 decrease in expression from baseline to follow-up by residual disease of 39 paired samples. PD-L1 percent decrease from baseline to post-treatment are shown in the box plot classified by cases with pathologic complete response (pCR, n=15) or not (no pCR, n=24).
See this image and copyright information in PMC

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