Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape

Song, Saemee; Kim, Sehui; Koh, Jaemoon; Yim, Jeemin; Han, Bogyeong; Kim, Young A; Jeon, Yoon Kyung; Chung, Doo Hyun

doi:10.1007/s00262-020-02840-0

Cited by 48 publications

(86 citation statements)

References 43 publications

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“…Brain metastasis lesion had a lower immune-related pathway score and the proportion of the immune cell subsets than the primary lung cancer. Conversely, the immunosuppressive pathway, the TGF-β pathway, was enriched in BM [29]. In general, both NSCLC BM tissues and adjacent noncancer brain tissues are in an immunosuppressive environment [30].…”

Section: The Rationale Of the Application Of Icis In Nsclc Bmmentioning

confidence: 97%

“…Compared with EGFR wild-type lung adenocarcinoma BM, several immune-related pathways were upregulated in EGFR-mutant samples. EGFR mutation may transform the tumor immune microenvironment of brain metastatic lung adenocarcinoma into a more active phenotype [29]. Consequently, in lung adenocarcinoma BM, EGFR-mutated patients may benefit from immunotherapy.…”

Section: The Rationale Of the Application Of Icis In Nsclc Bmmentioning

confidence: 99%

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Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

et al. 2021

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Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.

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Section: The Rationale Of the Application Of Icis In Nsclc Bmmentioning

confidence: 97%

Section: The Rationale Of the Application Of Icis In Nsclc Bmmentioning

confidence: 99%

Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

et al. 2021

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“…Cancer is a complex and heterogeneous disease that involves the dysregulation of various cell processes, such as metabolism ( 19 ), proliferation ( 20 ), intracellular pH dynamics ( 21 ), redox signaling ( 22 ), and migration/invasion ( 23 , 24 ). The complexity of this disease is also reflected by the different ecosystems that constitute a permissive TME ( 25 , 26 ). A close inspection of the TME reveals a network of cellular and non-cellular components that provide the signals that control tumor cell survival, proliferation, angiogenesis, immune evasion and metastasis.…”

Section: Immunological Tumor Microenvironmentmentioning

confidence: 99%

The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment

2021

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The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be used for different biomedical applications, it is important to know how they affect the immune system and its different cell types, especially their interaction with the macrophages that are involved in their clearance. How immune cells respond to therapeutic interventions can condition the systemic and local tissue response, and hence, the final therapeutic outcome. Thus, it is fundamental to understand the effects that IONPs have on the immune response, especially in cancer immunotherapy. The biological effects of IONPs may be the result of intrinsic features of their iron oxide core, inducing reactive oxygen species (ROS) and modulating intracellular redox and iron metabolism. Alternatively, their effects are driven by the nanoparticle coating, for example, through cell membrane receptor engagement. Indeed, exploiting these properties of IONPs could lead to the development of innovative therapies. In this review, after a presentation of the elements that make up the tumor immunological microenvironment, we will review and discuss what is currently known about the immunomodulatory mechanisms triggered by IONPs, mainly focusing on macrophage polarization and reprogramming. Consequently, we will discuss the implications of these findings in the context of plausible therapeutic scenarios for cancer immunotherapy.

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“…6. As for the EGFR protein, Song [7] described its characteristics in R language in the immune microenvironment of the brain metastases of lung cancer. We found that mutant EGFR protein tends to cluster together in the brain, in a pattern that is different from the one resulting from the up regulation of various immune-related pathways of brain metastases.…”

Section: Molecular Pathologymentioning

confidence: 99%

“…We have built on previous knowledge of TTF1 and EGFR in brain metastases of lung cancer [2,7,8]. We performed extensive literature searches, given preliminarily evidence that GBP4 could be used as a key regulatory protein of HCMV infection in brain metastases of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

Zhao

et al. 2021

Preprint

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Background: The links between brain metastases of lung cancer and human cytomegalovirus (HCMV) infection have been controversial for a long time. This study aims to explore the links between brain metastases of lung cancer and HCMV infection from the perspective of expression and detection of HCMV immediate early gene (IE), guanine nucleotide-binding protein 4 (GBP4), CXC chemokine receptor 4 (CXCR4), thyroid transcription factor 1 (TTF1) and epidermal growth factor receptor (EGFR) proteins. Methods: We collected brain metastases specimens and lung primary tumor specimens of a series of patients that have not undergone any treatment. Conventional hematoxylin and eosin staining and immunohistochemical staining of target molecules was performed. We used the ImageJ software to process the average optical density value of immune complexes and GraphPad Prism 8.0.1 to perform image analysis, and the SPSS 22.0 statistics package (t test) to analyze the expression differences of target molecules.Results: Based on five cases of brain metastases and two cases of lung primary tumors, a total of seven samples were investigated. Conventional pathology diagnosis reported four cases of brain metastases of lung adenocarcinoma and one case of brain metastases of mixed small cell lung cancer with adenocarcinoma. Among the 19 molecular immunopathological test samples, only GBP4, related to HCMV infection, and TTF1, related to metastases, were highly expressed in all seven samples. A comparison of the AOD values of the primary lung cancer to the AOD values of brain metastases, yielded statistically significant differences as follows: in Case No.1, GBP4 (p=0.016), EGRF (p<0.001); in Case No. 2, IE (p<0.001), CXCR4 (p=0.005), EGFR (p=0.023), TTF1 (p=0.004). Conclusions: Although TTF1 is known to be a kinesin for brain metastases of lung cancer cells and it is associated with poor survival prognosis, the role of GBP4, which is closely related to HCMV infection and a key protein of brain metastases of lung cancer, remains unknown. The findings provide new knowledge into the role of GBP4 and could provide clues for devising novel strategies for target molecular therapy research in brain metastases of lung cancer in the context of HCMV infection.

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Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape

Cited by 48 publications

References 43 publications

Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment

Expression of Five Target Proteins Related to Human Cytomegalovirus Infection in Brain Metastases of Lung Cancer

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