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Research article
Bo Yang
Department of Oncology, Chinese PLA General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8989-9387
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Tumor mutation burden (TMB) is associated with the formation of tumors and the outcomes of immunotherapy, especially in non-small cell lung cancers (NSCLC). The aim of this study was to study immune features of NSCLC with different mutation burdens. We performed a comprehensive comparison of immune features, including driver mutations, up- or down-regulated expression of key biological pathways, tumor cell evolution, tumor cell stemness, etiology, and immune cell infiltration, between ultra-low (UL) and ultra-high (UH) TMB NSCLC.
Results: Generally, we found that UL-TMB tumors contained a higher proportion of driver mutations and maintained an “immune-desert” tumor microenvironment with reduced effector cell infiltration and increased suppressor cell infiltration. In UH-TMB tumors, the expression levels of cell cycles, DNA replication and mismatch repair pathways were up-regulated. We discovered that UL-TMB tumors had different up-regulated pathways between a denocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Basically, the expression levels of primary bile acid biosynthesis, arachidonic acid metabolism, and drug metabolism pathways were up-regulated in LUAD; however, the expression level of CaM pathway and the PLC-gamma1 signaling pathway were up-regulated in LUSC. Most mutations in UH-TMB tumors occurred in the early stages, while UL-TMB tumors showed the opposite trend. UH-TMB tumors had a relatively high stemness score. Despite the mutations and neo-antigens increasing in UH-TMB tumors, the overall antigen presentation capacity was weak.
Conclusions: These results support rational design of therapeutic strategies for NSCLC with different mutation burdens.
Keywords
Non-small cell lung cancer, Tumor mutation burden, Tumor microenvironment
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Bo Yang
Department of Oncology, Chinese PLA General Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8989-9387
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 23 Jul, 2020
No community comments so far
Community comments: 1
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Tumor mutation burden (TMB) is associated with the formation of tumors and the outcomes of immunotherapy, especially in non-small cell lung cancers (NSCLC). The aim of this study was to study immune features of NSCLC with different mutation burdens. We performed a comprehensive comparison of immune features, including driver mutations, up- or down-regulated expression of key biological pathways, tumor cell evolution, tumor cell stemness, etiology, and immune cell infiltration, between ultra-low (UL) and ultra-high (UH) TMB NSCLC.
Results: Generally, we found that UL-TMB tumors contained a higher proportion of driver mutations and maintained an “immune-desert” tumor microenvironment with reduced effector cell infiltration and increased suppressor cell infiltration. In UH-TMB tumors, the expression levels of cell cycles, DNA replication and mismatch repair pathways were up-regulated. We discovered that UL-TMB tumors had different up-regulated pathways between a denocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Basically, the expression levels of primary bile acid biosynthesis, arachidonic acid metabolism, and drug metabolism pathways were up-regulated in LUAD; however, the expression level of CaM pathway and the PLC-gamma1 signaling pathway were up-regulated in LUSC. Most mutations in UH-TMB tumors occurred in the early stages, while UL-TMB tumors showed the opposite trend. UH-TMB tumors had a relatively high stemness score. Despite the mutations and neo-antigens increasing in UH-TMB tumors, the overall antigen presentation capacity was weak.
Conclusions: These results support rational design of therapeutic strategies for NSCLC with different mutation burdens.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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