Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial
| Autor: | Brad Wasserman, David L. Rimm, Debasish Tripathy, Zeina Nahleh, Daniel F. Hayes, Peggy L. Porter, Ying-Chun Lo, Vasiliki Pelekanou, William E. Barlow, Julie Gralow, Marie Kristin von Wahlde, Lajos Pusztai, Gabriel N. Hortobagyi, Borbála Székely, Christos Hatzis |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Bevacizumab Cyclophosphamide medicine.medical_treatment Lymphocyte chemical and pharmacologic phenomena Breast Neoplasms B7-H1 Antigen Article 03 medical and health sciences 0302 clinical medicine Clinical Trials Phase II as Topic Lymphocytes Tumor-Infiltrating Internal medicine Biomarkers Tumor Medicine Humans Lymphocyte Count Neoadjuvant therapy Chemotherapy business.industry Tumor-infiltrating lymphocytes Cancer hemic and immune systems medicine.disease Prognosis Immunohistochemistry Neoadjuvant Therapy Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Chemotherapy Adjuvant 030220 oncology & carcinogenesis Female business Adjuvant medicine.drug |
| Zdroj: | Molecular cancer therapeutics. 17(6) |
| ISSN: | 1538-8514 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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