Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

OncoImmunology

Michèle Beau-Faller¹  Pierre Laurent-Puig¹  Hélène Blons¹  Claire Danel²  Jacques Cadranel³  Marie Wislez³  Laure Gibault⁴  Françoise Le Pimpec Barthes⁴  Patrick Bruneval⁴  Elisabeth Fabre⁴  Paul Hofman⁵  Lucie Biard⁶  Martine Antoine⁷  Marion Mandavit⁸  Eric Tartour⁸  Eléonore De Guillebon⁸  Hélène Roussel⁸  Clémence Granier⁸  Stéphane Oudard⁸  Alain Gey⁸  Cécile Badoual⁸ 

[1] Department of Biochemistry and Molecular Biology;Department of Pathology Pompidou;GRC04 Théranoscan, Université P&M Curie;Hôpital Européen Georges Pompidou;Hôpital Pasteur;Hôpital Saint Louis;Hôpital Tenon;INSERM U970, Université Paris Descartes, Sorbonne Paris Cité;

关键词: alk-positive adenocarcinoma;    immunotherapy;    in situ quantitative cell imaging;    predictive biomarker;    tumor microenvironment;   

DOI  :  10.1080/2162402X.2017.1286437

来源: DOAJ

【 摘 要 】

Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8+ T cells expressing PD-1. To more effectively integrate all of these potential biomarkers of clinical response to immunotherapy, we have developed a multiparametric immunofluorescence technique with automated immune cell counting to comprehensively analyze the tumor microenvironment of ALK-positive adenocarcinoma (ADC). When analyzed as either a continuous or a dichotomous variable, the mean number of tumor cells expressing PD-L1 (p = 0.012) and the percentage of tumor cells expressing PD-L1 were higher in ALK-positive ADC than in EGFR-mutated ADC or WT (non-EGFR-mutated and non-KRAS-mutated) NSCLC. A very strong correlation between PD-L1 expression on tumor cells and intratumoral infiltration by CD8+ T cells was observed, suggesting that an adaptive mechanism may partly regulate this expression. A higher frequency of tumors combining positive PD-L1 expression and infiltration by intratumoral CD8+ T cells or PD-1+CD8+ T cells was also observed in ALK-positive lung cancer patients compared with EGFR-mutated (p = 0.03) or WT patients (p = 0.012). These results strongly suggest that a subgroup of ALK-positive lung cancer patients may constitute good candidates for anti-PD-1/-PD-L1 therapies.

【 授权许可】

Unknown