Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial
| Autor: | Tadeusz Pienkowski, A. Lluch, Luca Gianni, Domenico Magazzu, Jose Luiz Pedrini, Brigitte Poirier, D-Y. Oh, P. Valagussa, Lajos Pusztai, Vladimir Semiglazov, Eugenia Galeota, Giampaolo Bianchini, J. de la Haba-Rodríguez, L-M Tseng, MC Liu, Yunjoo Im, Giulia Valeria Bianchi |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Receptor ErbB-2 medicine.drug_class Lymphocyte Breast Neoplasms chemical and pharmacologic phenomena Antibodies Monoclonal Humanized Monoclonal antibody Young Adult Immune system Trastuzumab Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Aged 80 and over Immunity Cellular Predictive marker biology business.industry Antibodies Monoclonal Hematology Middle Aged Chemotherapy regimen Neoadjuvant Therapy Treatment Outcome medicine.anatomical_structure Oncology Cancer research biology.protein Female Pertuzumab Antibody business medicine.drug |
| Zdroj: | Annals of Oncology. 26:2429-2436 |
| ISSN: | 0923-7534 |
| Popis: | Background To investigate in the NeoSphere trial the contribution of the immune system to pathologic complete response in the breast (pCRB) after neoadjuvant docetaxel with trastuzumab (TH), pertuzumab (TP), or both (THP), or monoclonal antibodies alone (HP). Patients and methods Immune gene mRNA expression (n = 350, 83.8%), lymphocyte infiltration (TIL, n = 243, 58.3%), and PDL1 by immunohistochemistry (n = 305, 73.1%) were correlated with pCRB. We studied five selected genes (IFNG, PD1, PDL1, PDL2, CTLA4) and six immune metagenes corresponding to plasma cells (IGG), T cells (CD8A), antigen-presenting cells (MHC2), and to MHC1 genes (MHC1), STAT1 co-expressed genes (STAT1), and interferon-inducible genes (IF-I). Gene expression data from the NOAH trial were used for validation. Results TIL as continuous variable and PDL1 protein expression were not significantly associated with pCRB. Expression of immune genes/metagenes had different association with pCRB after THP than after other therapies. With THP, higher expression of PD1 and STAT1, or any among PDL1, CTLA4, MHC1, and IF-I were linked with lower pCRB. In the combined TH/TP/HP treatment group, in multivariate analysis, higher expression of PD1, MHC2, and STAT1 were linked with pCRB, and higher PDL1, MHC1, or IF-I to lower pCRB. In the NOAH, a similar association of higher STAT1 with higher pCRB, and higher MHC1 and IF-I with lower pCRB was found for trastuzumab/chemotherapy but not for chemotherapy treatment only. Conclusions The immune system modulates response to therapies containing trastuzumab and pertuzumab. Greatest benefit from THP is observed for low expression of some immune markers (i.e. MHC1, CTLA4). The involvement of PDL1 in resistance supports testing combinations of HER2-directed antibodies and immune-checkpoint inhibitors. |
| Databáze: | OpenAIRE |
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