Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes

Doroshow, Deborah Blythe; Sanmamed, Miguel F.; Hastings, Karen Taraszka; Politi, Katerina; Rimm, David L.; Chen, Lieping; Melero, Ignacio; Schalper, Kurt A.; Herbst, Roy S.

doi:10.1158/1078-0432.ccr-18-1538

Cited by 510 publications

(472 citation statements)

References 99 publications

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“…4 Herein, we initially identify MTHFD2 is significantly up-regulated in NSCLC as a potential oncogene. 4 Herein, we initially identify MTHFD2 is significantly up-regulated in NSCLC as a potential oncogene.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Chang

Yang

Cai

et al. 2019

J Cellular Molecular Medi

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Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. It has been reported to be overexpressed in several malignancies. However, the relationship between the expression of MTHFD2 and non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that MTHFD2 was significantly overexpressed in NSCLC tissues and cell lines. Knockdown of MTHFD2 resulted in reduced cell growth and tumorigenicity in vitro and in vivo. Besides, the mRNA and protein expression level of cell cycle genes, such as CCNA2, MCM7 and SKP2, was decreased in MTHFD2 knockdown H1299 cells. Our results indicate that the inhibitory effect of MTHFD2 knockdown on NSCLC may be mediated via suppressing cell cycle-related genes. These findings delineate the role of MTHFD2 in the development of NSCLC and may have potential applications in the treatment of NSCLC. K E Y W O R D S bioinformatics, cell cycle, methylenetetrahydrofolate dehydrogenase 2, non-small cell lung cancer | 1569 YU et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Yu C, Yang L, Cai M, et al. Downregulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes. J Cell Mol Med.

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Section: Discussionmentioning

confidence: 99%

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Chang

Yang

Cai

et al. 2019

J Cellular Molecular Medi

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Section: Discussionmentioning

confidence: 99%

“…At present, research on the clinical diagnosis and treatment of lung cancer, combined with the treatment strategies of immunotherapy, targeted therapy, and chemotherapy, is becoming a new focus in research. 12 There is an urgent requirement to identify novel molecular markers and therapeutic targets. CircRNA is characterized by abundant expression and conservation, stable expression in saliva, blood, and exosomes, and CircRNA exhibits specificity at the stage of tissue development.…”

Section: Discussionmentioning

confidence: 99%

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Xiang

Chen

et al. 2020

Thoracic Cancer

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Background Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ‐IGF1R) in non‐small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ‐IGF1R in lung cancer. Methods We screened circ‐IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ‐IGF1R was examined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound‐healing and Transwell assays were used for verifying the biological function of circ‐IGF1R. The effect of overexpressing circ‐IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA‐seq. Results The expression level of circ‐IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P < 0.0001). In addition, the expression level of circ‐IGF1R was associated with larger tumors (T2/T3/T4) and lymph node metastasis (N1/ N2/N3) (P < 0.05). The overexpression of circ‐IGF1R significantly inhibited the invasion and migration of the lung cancer cells. The potential network of circ‐IGF1R–miR‐1270–VANGL2 was preliminarily determined, and the expression patterns of miR‐1270 and VANGL2 were verified in lung cancer cell lines. Conclusion Circ‐IGF1R may inhibit lung cancer invasion and migration through a potential network of circ‐IGF1R–miR‐1270–VANGL2.

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“…In a recent retrospective analysis of five patients with new or progressing brain metastases from NSCLC treated with PD-1 blockade, an objective response was observed in two patients and persisted for greater than six months, suggesting a possible role for anti-PD-1 therapy in treating CNS metastases [25][26][27] . While these findings are very encouraging, most PD-L1 expression positive primary NSCLC patients were failed to respond to conventional immune checkpoint therapy, let alone the ones without PD-L1 expression 28,29 . The design of immunomodulatory strategies for the treatment of NSCLC patients with a metastatic brain tumor will tremendously benefit from a detailed understanding of the immune cell landscape that develops specifically in response to tumor cues 30 .…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Map of Diverse Immune Phenotypes in the Metastatic Brain Tumor Microenvironment of Non Small Cell Lung Cancer

Wang

Dai

Han

et al. 2019

Preprint

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Cancer immunotherapies have shown sustained clinical success in treating primary nonsmall-cell lung cancer (NSCLC). However, patients with brain metastasis are excluded from the trials because the brain is viewed traditionally as an immune-privileged organ. The composition and properties of tumor-infiltrating myeloid cells in metastatic brain tumors are mostly unknown. To depict the baseline landscape of the composition, gene signature, and functional states of these immune cells, we performed -single-cell RNA sequencing (scRNAseq) for 12,196cellsafter data preprocessing, including 2,241 immunecells from three surgically removed brain lesions of treatment-naïve NSCLC patients. We found a lack of T lymphocyte infiltration and activation, as well as the vast expansion of tumor-associated macrophage(TAM) in the brain lesions of NSCLC patients. By comparing our scRNAseq dataset with published data from early and late-stage primary NSCLC tumors, we showed that this compromised T cell response is unique to brain lesions. We identified a unique alternative activation (M2) gene expression pattern of the TAM in the brain metastasis and a lack of known T cell co-stimulator expression. Accumulation of M2 polarized TAM may, therefore, cause the comprised anti-tumor T cell response in metastatic brain lesions. These findings can contribute to the design of new immunotherapy strategies for NSCLC patients with brain metastasis.

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Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes

Cited by 510 publications

References 99 publications

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Single-Cell Map of Diverse Immune Phenotypes in the Metastatic Brain Tumor Microenvironment of Non Small Cell Lung Cancer

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