Although the recurrence of EGC is very rare in general, EGC with lymph node metastasis has a higher possibility of recurring, especially with >6 positive lymph nodes. Even after curative resection of EGC, patients with EGC with >6 positive lymph nodes should be closely followed and be considered as candidates for adjuvant treatment.

The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples. We used the information to predict subtype-specific interactions within the LUSC microenvironment and to connect genomic alterations with immune signatures. Hierarchical clustering based on gene expression and mutational profiling revealed subtypes that were either immune defective or immune competent. We analyzed infiltrating stromal and immune cells to further characterize the tumor microenvironment. Elevated expression of macrophage 2 signature genes in the immune competent subtype confirmed that tumor-associated macrophages (TAM) linked inflammation and mutation-driven cancer. A negative correlation was evident between the immune score and the amount of somatic copy-number variation (SCNV) of immune genes ( = -0.58). The SCNVs showed a potential detrimental effect on immunity in the immune-deficient subtype. Knowledge of the genomic alterations in the tumor microenvironment could be used to guide design of immunotherapy options that are appropriate for patients with certain cancer subtypes. .

The metabolic properties of tumor microenvironment (TME) are dynamically dysregulated to achieve immune escape and promote cancer cell survival. However, in vivo properties of glucose metabolism in cancer and immune cells are poorly understood and their clinical application to development of a biomarker reflecting immune functionality is still lacking. Methods: We analyzed RNA-seq and fluorodeoxyglucose (FDG) positron emission tomography profiles of 63 lung squamous cell carcinoma (LUSC) specimens to correlate FDG uptake, expression of glucose transporters (GLUT) by RNA-seq and immune cell enrichment score (ImmuneScore). Single cell RNA-seq analysis in five lung cancer specimens was performed. We tested the GLUT3/GLUT1 ratio, the GLUT-ratio, as a surrogate representing immune metabolic functionality by investigating the association with immunotherapy response in two melanoma cohorts. Results: ImmuneScore showed a negative correlation with GLUT1 ( r = -0.70, p < 0.01) and a positive correlation with GLUT3 ( r = 0.39, p < 0.01) in LUSC. Single-cell RNA-seq showed GLUT1 and GLUT3 were mostly expressed in cancer and immune cells, respectively. In immune-poor LUSC, FDG uptake was positively correlated with GLUT1 ( r = 0.27, p = 0.04) and negatively correlated with ImmuneScore ( r = -0.28, p = 0.04). In immune-rich LUSC, FDG uptake was positively correlated with both GLUT3 ( r = 0.78, p = 0.01) and ImmuneScore ( r = 0.58, p = 0.10). The GLUT-ratio was higher in anti-PD1 responders than nonresponders ( p = 0.08 for baseline; p = 0.02 for on-treatment) and associated with a progression-free survival in melanoma patients who treated with anti-CTLA4 ( p = 0.04). Conclusions: Competitive uptake of glucose by cancer and immune cells in TME could be mediated by differential GLUT expression in these cells.

No abstract

No abstract