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

Abstract

The tumor microenvironment consists of an intricately organized system through which immune cells and cancer cells may communicate to regulate antitumor 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 immuneexcluded tumors within LUAD and LUSC were not subtype specific. Instead, immuneinflamed 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.

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

“…Besides, the KEGG pathway enrichment displayed that the DEGs mostly clustered in the Cytokine−cytokine receptor interaction, the Chemokine signaling pathway, and the Viral protein interaction with cytokine and cytokine receptor. Consistent with these results, previous studies have shown that the biological processes of the immune system are critical to the formation of a complicated LUAD tumor microenvironment 10,30,[37][38][39] . In the past few years, the understanding of the immunological characteristics of LUAD has increased, and the development of effective LUAD immunotherapy strategies has drawn wide attention [40][41][42][43][44] .…”

Mine TCGA Database for Tumor Microenvironment-Related Genes of Prognostic value in lung squamous cell carcinoma

“…Zeng et al provides potential TME-related biomarker for the therapy and prognosis of RCC [34].Zeng et al describe the comprehensive features of gastric cancer TME characteristics and provide new strategies for cancer treatment [35].A present study found that many elements of TME other than tumor epithelial cells influence the progression of HNSCC [36]. Another study highlights the favorable prognostic impact of an immune-inflamed TME in LUAD [37]. There is also studies analyzed the immune microenvironment of stage I LUAD and found that the high expression of IL-7R and the lower expression of IL-12Rβ2 were all independent factors of poor prognosis [38].Yue et al identified three TME-related DEGs signature which could be used to predict the prognosis of LUAD patients [39].Chen et al revealed the differentiated regulation of immuneresponse related genes between LUAD and LUSC [28].…”

Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development

“…In this study, we demonstrate that immune cell specific PTPN2 plays an important role in the development of human CRC. Using a large collective of tissue samples from CRC patients, we show that PTPN2 protein expression and activity was highly elevated in human CRC tissue, with a marked increase in immune cells, and that high Since in the majority of CRC patients, low immunogenicity of the tumors prevents response to immunotherapies (7,8,25,26), therapeutic approaches that promote the immunogenic potential provide a strong rationale for improving treatment success. Our data from primary and metastatic human CRC tissues indicate a strong correlation of local PTPN2 expression and reduced immune response.…”

“…In 2018, more than 1.8 million patients were newly diagnosed with CRC and despite improved 5-year survival, the estimated number of CRC-related deaths accumulated to 881,000 (3)(4)(5)(6). Successful immunotherapeutic interventions in other solid cancers, such as melanoma and lung carcinoma have exploited their tumor microenvironment, which contains high numbers of immune cells, such as T-cells, natural killer (NK) cells and antigen-presenting cells (7,8). The majority of CRC, however, lack prominent immune infiltrates and only about 4% of all CRC cases respond to immunotherapies (2,9).…”