Increased tumor glycolysis is associated with decreased immune infiltration across human solid tumors Journal Article
| Authors: | Cohen, I. J.; Pareja, F.; Socci, N. D.; Shen, R.; Doane, A. S.; Schwartz, J.; Khanin, R.; Morris, E. A.; Sutton, E. J.; Blasberg, R. G. |
| Article Title: | Increased tumor glycolysis is associated with decreased immune infiltration across human solid tumors |
| Abstract: | Response to immunotherapy across multiple cancer types is approximately 25%, with some tumor types showing increased response rates compared to others (i.e. response rates in melanoma and non-small cell lung cancer (NSCLC) are typically 30-60%). Patients whose tumors are resistant to immunotherapy often lack high levels of pre-existing inflammation in the tumor microenvironment. Increased tumor glycolysis, acting through glucose deprivation and lactic acid accumulation, has been shown to have pleiotropic immune suppressive effects using in-vitro and in-vivo models of disease. To determine whether the immune suppressive effect of tumor glycolysis is observed across human solid tumors, we analyzed glycolytic and immune gene expression patterns in multiple solid malignancies. We found that increased expression of a glycolytic signature was associated with decreased immune infiltration and a more aggressive disease across multiple tumor types. Radiologic and pathologic analysis of untreated estrogen receptor (ER)-negative breast cancers corroborated these observations, and demonstrated that protein expression of glycolytic enzymes correlates positively with glucose uptake and negatively with infiltration of CD3+ and CD8+ lymphocytes. This study reveals an inverse relationship between tumor glycolysis and immune infiltration in a large cohort of multiple solid tumor types. Copyright © 2022 Cohen, Pareja, Socci, Shen, Doane, Schwartz, Khanin, Morris, Sutton and Blasberg. |
| Keywords: | immunohistochemistry; adult; cancer survival; clinical article; controlled study; human tissue; protein expression; aged; survival analysis; gene mutation; human cell; overall survival; positron emission tomography; cd3 antigen; cd8 antigen; cd8+ t lymphocyte; tumor associated leukocyte; mass spectrometry; melanoma; breast cancer; gene expression; cell infiltration; tumor volume; carcinoma, non-small-cell lung; lung neoplasms; cohort analysis; cytotoxicity; immunoreactivity; breast neoplasms; proteomics; protein p53; lung tumor; correlation analysis; immunotherapy; breast tumor; lymph node; cd4+ t lymphocyte; androgen receptor; lactate dehydrogenase; cd4 antigen; estrogen receptor; cd3+ t lymphocyte; bioinformatics; b raf kinase; glucose transport; glycolysis; fluorodeoxyglucose; t lymphocyte subpopulation; pleiotropy; cutaneous melanoma; immunosuppressive agent; solid tumors; breast lesion; lactic acid; programmed death 1 ligand 1; programmed death 1 receptor; non small cell lung cancer; tumor microenvironment; glycolytic enzyme; metabolomics; tumor metabolism; cancer prognosis; estrogen receptor positive breast cancer; immune infiltration; humans; human; male; female; article; estrogen receptor negative breast cancer; gene set enrichment analysis; positron emission tomography-computed tomography; solid malignant neoplasm; mrna expression level; multiple tumor |
| Journal Title: | Frontiers in Immunology |
| Volume: | 13 |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2022-11-24 |
| Start Page: | 880959 |
| Language: | English |
| DOI: | 10.3389/fimmu.2022.880959 |
| PUBMED: | 36505421 |
| PROVIDER: | scopus |
| PMCID: | PMC9731115 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2023 -- Source: Scopus |
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