An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma

// Kevin B. Givechian 1 , Chad Garner 2 , Steve Benz 1 , Bing Song 1 , Shahrooz Rabizadeh 1, 2 and Patrick Soon-Shiong 1, 2, 3 1 NantOmics LLC, Culver City, CA 90232, USA 2 NantHealth, Inc. NantWorks, Culver City, CA 90232, USA 3 NantBioscience, Inc. NantWorks, Culver City, CA 90232, USA Correspondence to: Kevin B. Givechian, email: Kevin.Givechian@nantomics.com Keywords: NSCLC; lung adenocarcinoma; lung squamous cell carcinoma; tumor immunology; tumor microenvironment Abbreviations: NSCLC: non-small cell lung cancer; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; OS: overall survival; TME: tumor microenvironment Received: January 25, 2019 Accepted: February 15, 2019 Published: March 05, 2019 ABSTRACT The tumor microenvironment consists of an intricately organized system through which immune cells and cancer cells may communicate to regulate anti-tumor immunogenicity. To this end, non-small cell lung cancer (NSCLC) has been shown to activate a variety of immunological mechanisms, thereby broadening our understanding of lung cancer immunobiology. However, while recent work has highlighted the importance of NSCLC immunology and prognosis, studies have not yet examined the tumor microenvironment (TME) globally in regards to the survival outcomes between two major NSCLC subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present study, we identify an immunogenic tumor microenvironment state in NSCLC that is enriched for the lung adenocarcinoma subtype. By utilizing TME cell enrichment scores and RNA-seq expression data, we show that the inflamed TME is associated with favorable patient survival in lung adenocarcinoma, but this does not hold true for lung squamous cell carcinoma. Moreover, differentially regulated pathways between immune-inflamed and immune-excluded tumors within LUAD and LUSC were not subtype specific. Instead, immune-inflamed LUSC samples possessed elevated immune checkpoint marker expression when compared to those of the LUAD samples, thereby offering a putative explanation for our prognostic observations. These results shed light on the immunological prognostic effects within lung cancer and may encourage further TME exploration between these two subtypes as the landscape of NSCLC therapy progresses.