Tumor microenvironment as a potential source of clinical biomarkers in non-small cell lung cancer: can we use enemy territory at our advantage?

Genova, Carlo; Rijavec, Erika; Grossi, Francesco

doi:10.21037/jtd.2017.10.66

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…The matrix, a highly abundant component of tumors, could be considered as a good tumor biomarker as matrix is often more stable than e.g., antigens expressed by tumor cells ( 70 , 71 ). Furthermore, matrix seems to be accessible to antibodies and antibody derivatives in therapy ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

et al. 2021

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The extracellular matrix (ECM) molecule Tenascin-C (TNC) is well-known to promote tumor progression by multiple mechanisms. However, reliable TNC detection in tissues of tumor banks remains limited. Therefore, we generated dromedary single-domain nanobodies Nb3 and Nb4 highly specific for human TNC (hTNC) and characterized the interaction with TNC by several approaches including ELISA, western blot, isothermal fluorescence titration and negative electron microscopic imaging. Our results revealed binding of both nanobodies to distinct sequences within fibronectin type III repeats of hTNC. By immunofluroescence and immunohistochemical imaging we observed that both nanobodies detected TNC expression in PFA and paraffin embedded human tissue from ulcerative colitis, solid tumors and liver metastasis. As TNC impairs cell adhesion to fibronectin we determined whether the nanobodies abolished this TNC function. Indeed, Nb3 and Nb4 restored adhesion of tumor and mesangial cells on a fibronectin/TNC substratum. We recently showed that TNC orchestrates the immune-suppressive tumor microenvironment involving chemoretention, causing tethering of CD11c+ myeloid/dendritic cells in the stroma. Here, we document that immobilization of DC2.4 dendritic cells by a CCL21 adsorbed TNC substratum was blocked by both nanobodies. Altogether, our novel TNC specific nanobodies could offer valuable tools for detection of TNC in the clinical practice and may be useful to inhibit the immune-suppressive and other functions of TNC in cancer and other diseases.

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Section: Discussionmentioning

confidence: 99%

Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

et al. 2021

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“…Immunological changes occurring during the process of cancer procession and metastatic nodule formation include the expansion of immunosuppressive cells, expression of cytokines and chemokines, lymphangiogenesis, and blood vessel remodeling [23,24]. Indeed, much attention has been paid to TME characterization of the primary tumor in previous reports [25,26]. However, the TME landscape in lymphatic metastases and its prognostic relevance in locally advanced LUAD patients may have been underestimated.…”

Section: Discussionmentioning

confidence: 99%

Tumor Immune Microenvironment Characterization of Primary Lung Adenocarcinoma and Lymph Node Metastases

Zhou

Shi

Chen

et al. 2021

BioMed Research International

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Background. The essential roles of the tumor microenvironment (TME) have been recognized during the initiation and progression of primary lung adenocarcinoma (LUAD). The aim of the present study was to delineate the immune landscape in both primary cancer and matched lymph node metastasis from a cohort of locally advanced stage LUAD patients with distinct outcomes. Methods. Formalin-fixed, paraffin-embedded samples were collected from 36 locally advanced LUAD patients. Transcriptome data of the tumor immune microenvironment were resolved using an immune oncology panel RNA sequencing platform. Bioinformatics approaches were used to determine the differentially expressed genes (DEGs), dysregulated pathways, and immune cell fraction between patients with early recurrence (ER) and late recurrence (LR). Results. Here, we showed that in primary cancer tissues, 23 DEGs were obtained between patients with ER and LR. Functional analysis revealed that the LR in LUAD patients may be associated with enriched gene sets belonging to the antigen presentation and MHC protein complex, innate immune response, and IFN-γ signaling pathways. Next, the transcriptome data were adopted to quantify immune cell fractions, indicating that high infiltration of mast cells and neutrophils was correlated with ER. Interestingly, similar findings were observed in metastatic lymph nodes from patients suffering from ER or LR. By analyzing the shared immune features of primary cancers and lymphatic metastases, we unraveled the prognostic value and joint utility of two DEGs, CORO1A and S100A8. Conclusions. In LUAD, the enrichment in antigen presentation, MHC protein complex, and IFN-γ signaling, and low infiltration of neutrophils in primary or metastatic nodules may be indications for a favorable prognosis. Integrated with bioinformatics approaches, transcriptome data of immune-related genes from formalin-fixed, paraffin-embedded (FFPE) samples can effectively profile the landscape of the tumor immune microenvironment and help predict clinical outcomes.

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“…S100A10 is a novel gene that may have potential as a biomarker and treatment target due to its persistent overexpression in a variety of tumor cells, as well as its contribution to several key hallmarks of cancer. Recently, S100A10 expression has been recognized as a potential malignancy biomarker in colorectal cancer (28), renal cell carcinoma (72), non-small cell lung carcinoma (90) and gallbladder cancer (91).…”

Section: Conclusion and Future Studiesmentioning

confidence: 99%

The prognostic value of S100A10 expression in cancer (Review)

et al. 2018

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S100A10, a member of the S100 protein family, commonly forms a heterotetrameric complex with Annexin A2. This is essential for the generation of cellular plasmin from plasminogen, which leads to a cascade of molecular events crucial for tumor progression. S100A10 upregulation has been reported in a number of cancers, suggesting that it may have potential as a prognostic biomarker, as well as predicting sensitivity to anticancer drugs. This review evaluates the direct and indirect relationships between S100A10 and cancer progression by investigating its role in cancer. Research papers published on PubMed and Google Scholar between 2007–2017 were collated and reviewed. We concluded that S100A10 affects the development of the hallmarks of cancer as explained by Hanahan and Weinberg in 2011, most notably by activating the invasion and metastasis of cancer cells. However, further studies are required to explore the underlying biological mechanisms of S100A10.

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Tumor microenvironment as a potential source of clinical biomarkers in non-small cell lung cancer: can we use enemy territory at our advantage?

Cited by 7 publications

References 26 publications

Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

Tumor Immune Microenvironment Characterization of Primary Lung Adenocarcinoma and Lymph Node Metastases

The prognostic value of S100A10 expression in cancer (Review)

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