Bertucci François, Finetti Pascal, Colpaert Cécile, Mamessier Emilie, Parizel Maxime, Dirix Luc, Viens Patrice, Birnbaum Daniel, van Laere Steven
Département d'Oncologie Moléculaire, "Equipe Labellisée Ligue Contre le Cancer", Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France.
Département d'Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France.
Oncotarget. 2015 May 30;6(15):13506-19. doi: 10.18632/oncotarget.3642.
We retrospectively analyzed PDL1 mRNA expression in 306 breast cancer samples, including 112 samples of an aggressive form, inflammatory breast cancer (IBC). PDL1 expression was heterogeneous, but was higher in IBC than in non-IBC. Compared to normal breast samples, PDL1 was overexpressed in 38% of IBC. In IBC, PDL1 overexpression was associated with estrogen receptor-negative status, basal and ERBB2-enriched aggressive subtypes, and clinico-biological signs of anti-tumor T-cell cytotoxic response. PDL1 overexpression was associated with better pathological response to chemotherapy, independently of histo-clinical variables and predictive gene expression signatures. No correlation was found with metastasis-free and overall specific survivals. In conclusion, PDL1 overexpression in IBC correlated with better response to chemotherapy. This seemingly counterintuitive correlation between expression of an immunosuppressive molecule and improved therapeutic response may be resolved if PDL1 expression is viewed as a surrogate marker of a strong antitumor immune response among patients treated with immunogenic chemotherapy. In such patients, PDL1 inhibition could protect activated T-cells or reactivate inhibited T-cells and improve the therapeutic response, notably when associated with immunogenic chemotherapy.
我们回顾性分析了306例乳腺癌样本中的PDL1 mRNA表达情况，其中包括112例侵袭性炎性乳腺癌（IBC）样本。PDL1表达具有异质性，但在IBC中高于非IBC。与正常乳腺样本相比，38%的IBC中PDL1过表达。在IBC中，PDL1过表达与雌激素受体阴性状态、基底样和富含ERBB2的侵袭性亚型以及抗肿瘤T细胞细胞毒性反应的临床生物学体征相关。PDL1过表达与化疗的更好病理反应相关，独立于组织临床变量和预测基因表达特征。未发现与无转移生存期和总体特异性生存期相关。总之，IBC中PDL1过表达与化疗的更好反应相关。如果将PDL1表达视为接受免疫原性化疗患者中强烈抗肿瘤免疫反应的替代标志物，那么这种免疫抑制分子表达与改善治疗反应之间看似违反直觉的相关性可能会得到解释。在此类患者中，PDL1抑制可保护活化的T细胞或重新激活受抑制的T细胞，并改善治疗反应，尤其是与免疫原性化疗联合使用时。
