Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response

Na, Kwon Joong; Choi, Hongyoon; Oh, Ho Rim; Kim, Yoon Ho; Lee, Sae Bom; Jung, Yoo Jin; Koh, Jaemoon; Park, Samina; Lee, Hyun Joo; Jeon, Yoon Kyung; Chung, Doo Hyun; Paeng, Jin Chul; Park, In Kyu; Kang, Chang Hyun; Cheon, Gi Jeong; Kang, Keon Wook; Lee, Dong Soo; Kim, Young Tae

doi:10.7150/thno.48954

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

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Theranostics 2020; 10(21):9579-9590. doi:10.7150/thno.48954 This issue Cite

Research Paper

Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response

Kwon Joong Na¹, Hongyoon Choi^2✉, Ho Rim Oh^3,4, Yoon Ho Kim³, Sae Bom Lee³, Yoo Jin Jung³, Jaemoon Koh⁵, Samina Park¹, Hyun Joo Lee¹, Yoon Kyung Jeon⁵, Doo Hyun Chung⁵, Jin Chul Paeng², In Kyu Park¹, Chang Hyun Kang¹, Gi Jeong Cheon^2,3, Keon Wook Kang^2,3, Dong Soo Lee², Young Tae Kim^1,3✉

1. Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
2. Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
3. Seoul National University Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
4. Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
5. Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.

Citation:

Na KJ, Choi H, Oh HR, Kim YH, Lee SB, Jung YJ, Koh J, Park S, Lee HJ, Jeon YK, Chung DH, Paeng JC, Park IK, Kang CH, Cheon GJ, Kang KW, Lee DS, Kim YT. Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response. Theranostics 2020; 10(21):9579-9590. doi:10.7150/thno.48954. https://www.thno.org/v10p9579.htm

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Abstract

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.

Keywords: tumor microenvironment, tumor metabolism, glucose transporter, immunotherapy, lung cancer, lung squamous cell carcinoma

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APA

Na, K.J., Choi, H., Oh, H.R., Kim, Y.H., Lee, S.B., Jung, Y.J., Koh, J., Park, S., Lee, H.J., Jeon, Y.K., Chung, D.H., Paeng, J.C., Park, I.K., Kang, C.H., Cheon, G.J., Kang, K.W., Lee, D.S., Kim, Y.T. (2020). Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response. Theranostics, 10(21), 9579-9590. https://doi.org/10.7150/thno.48954.

ACS

Na, K.J.; Choi, H.; Oh, H.R.; Kim, Y.H.; Lee, S.B.; Jung, Y.J.; Koh, J.; Park, S.; Lee, H.J.; Jeon, Y.K.; Chung, D.H.; Paeng, J.C.; Park, I.K.; Kang, C.H.; Cheon, G.J.; Kang, K.W.; Lee, D.S.; Kim, Y.T. Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response. Theranostics 2020, 10 (21), 9579-9590. DOI: 10.7150/thno.48954.

NLM

CSE

Na KJ, Choi H, Oh HR, Kim YH, Lee SB, Jung YJ, Koh J, Park S, Lee HJ, Jeon YK, Chung DH, Paeng JC, Park IK, Kang CH, Cheon GJ, Kang KW, Lee DS, Kim YT. 2020. Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response. Theranostics. 10(21):9579-9590.

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