Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy. (3rd April 2017)

• Record Type: Journal Article
• Authors: Roussel, Hélène; De Guillebon, Eléonore; Biard, Lucie; Mandavit, Marion; Gibault, Laure; Fabre, Elisabeth; Antoine, Martine; Hofman, Paul; Beau-Faller, Michèle; Blons, Hélène; Danel, Claire; Barthes, Françoise Le Pimpec; Gey, Alain; Granier, Clémence; Wislez, Marie; Laurent-Puig, Pierre; Oudard, Stéphane; Bruneval, Patrick; Badoual, Cécile; Cadranel, Jacques; Tartour, Eric
• Is Part Of: Oncoimmunology. Volume 6:Number 4(2017)
• Publication Date: 2017-04-03
• Subjects: ALK-positive adenocarcinoma -- immunotherapy -- in situ quantitative cell imaging -- predictive biomarker -- tumor microenvironment; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1286437
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.