bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2019–11–17
two papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge and Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Programmed cell death ligand-1-mediated enhancement of hexokinase 2 expression is inversely related to T-cell effector gene expression in non-small-cell lung cancer.
  2. HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma.
  1. J Exp Clin Cancer Res. 2019 Nov 12. 38(1): 462
    Programmed cell death ligand-1-mediated enhancement of hexokinase 2 expression is inversely related to T-cell effector gene expression in non-small-cell lung cancer.
    Sehui Kim, Ji-Young Jang, Jaemoon Koh, Dohee Kwon, Young A Kim, Jin Chul Paeng, Chan-Young Ock, Bhumsuk Keam, Miso Kim, Tae Min Kim, Dae Seog Heo, Doo Hyun Chung, Yoon Kyung Jeon.
       BACKGROUND: We investigated the role of PD-L1 in the metabolic reprogramming of non-small cell lung cancer (NSCLC).
    METHODS: Changes in glycolysis-related molecules and glycolytic activity were evaluated in PD-L1low and PD-L1high NSCLC cells after transfection or knockdown of PD-L1, respectively. Jurkat T-cell activation was assessed after co-culture with NSCLC cells. The association between PD-L1 and immune response-related molecules or glycolysis were analyzed in patients with NSCLC and The Cancer Genome Atlas (TCGA).
    RESULTS: Transfecting PD-L1 in PD-L1low cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. By contrast, knocking-down PD-L1 in PD-L1high cells decreased HK2 expression and glycolysis by suppressing PI3K/Akt and Erk pathways. Interferon-γ (IFNγ) secretion and activation marker expression was decreased in stimulated Jurkat T-cells when co-cultured with HK2-overexpressing vector-transfected tumor cells rather than empty vector-transfected tumor cells. Immunohistochemistry revealed that PD-L1 expression was positively correlated with HK2 expression in NSCLC (p < 0.001). In TCGA, HK2 exhibited a positive linear association with CD274 (PD-L1) expression (p < 0.001) but an inverse correlation with the expression of CD4, CD8A, and T-cell effector function-related genes in the CD274high rather than CD274low group. Consistently, there were fewer CD8+ T-cells in PD-L1positive/HK2high tumors compared to PD-L1positive/HK2low tumors in squamous cell carcinoma.
    CONCLUSIONS: PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. PD-L1 may contribute to NSCLC oncogenesis by inducing metabolic reprogramming and immune checkpoint.
    Keywords:  Glycolysis; Hexokinase 2; Non-small cell lung cancer; Programmed cell death-ligand-1; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s13046-019-1407-5
  2. Rev Assoc Med Bras (1992). 2019 ;pii: S0104-42302019001001295. [Epub ahead of print]65(10): 1295-1299
    HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma.
    Cigdem Usul Afsar, Pelin Uysal.
       AIM: To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT).
    METHODS: Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method.
    RESULTS: Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC.
    CONCLUSION: The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.
    DOI:  https://doi.org/10.1590/1806-9282.65.10.1295
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