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Mol Cancer Ther. 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.

Author information

1
Yale School of Medicine, Pathology, New Haven, Connecticut.
2
SWOG Statistical Center, Seattle, Washington.
3
Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas.
4
Yale School of Medicine, Medical Oncology, New Haven, Connecticut.
5
University of Michigan, School of Medicine, Medical Oncology, Ann Arbor, Michigan.
6
University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Fred Hutchinson Cancer Center, Seattle, Washington.
8
Yale School of Medicine, Medical Oncology, New Haven, Connecticut. lajos.pusztai@yale.edu.

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.

PMID:
29588392
PMCID:
PMC6548451
DOI:
10.1158/1535-7163.MCT-17-1005
[Indexed for MEDLINE]
Free PMC Article

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