The tumor microenvironment and immune targeting therapy in pediatric renal tumors

Hont, Amy; Dumont, Benoît; Sutton, Kathryn S.; Anderson, John; Kentsis, Alex; Drost, Jarno; Hong, Andrew L.; Verschuur, Arnauld

doi:10.1002/pbc.30110

Cited by 6 publications

(5 citation statements)

References 173 publications

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“…Surgical resection is the ideal method for treatment of KIRC patients, unfortunately a great number of patients are suffered from tumor recurrence after surgery ( 30 , 31 ). Currently, immunotherapy is an emerging direction for KIRC treatment ( 32 , 33 ). Therefore, finding new biomarkers associated with the immunomodulation is of significance for KIRC precision and personalized medicine.…”

Section: Discussionmentioning

confidence: 99%

OCLN as a novel biomarker for prognosis and immune infiltrates in kidney renal clear cell carcinoma: an integrative computational and experimental characterization

Jia,

Kong,

Wang

et al. 2023

Front. Immunol.

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BackgroundOccludin (OCLN) is an important tight junction protein and has been reported to be abnormally expressed in the development of malignant tumors. However, its biomarker and carcinogenic roles in kidney renal clear cell carcinoma (KIRC) are less investigated.MethodsThe Cancer Genome Atlas database and Human Protein Atlas database were used to analyze the expression of OCLN in KIRC. UALCAN database and methylation-specific PCR assay were used to evaluate the methylation level of OCLN in KIRC. Univariate and multivariate Cox regression analyses were performed to model the prognostic significance of OCLN in KIRC patient cohorts. The correlation between OCLN expression and the immune cell infiltration, immune-related function and immune checkpoints were explored. Finally, EdU, scratch assay and transwell experiments were conducted to validate the role of OCLN in KIRC development.ResultsThe expression of OCLN was significantly downregulated in KIRC, compared with normal renal tissues (p<0.001). Patients with low OCLN expression showed a worse prognosis and poorer clinicopathological characteristics. Functional enrichment analysis revealed that OCLN was mainly involved in biological processes such as immune response, immunoglobulin complex circulating and cytokine and chemokine receptor to mediate KIRC development. Immune-related analysis indicated that OCLN could potentially serve as a candidate target for KIRC immunotherapy. OCLN overexpression inhibited proliferation, migration and invasion of KIRC cells in vitro.ConclusionOCLN was validated as a candidate prognostic biomarker and therapeutic target of KIRC based both on computational and experimental approaches. More in vivo experiments will be conducted to decode its molecular mechanism in KIRC carcinogenesis in the future work.

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Section: Discussionmentioning

confidence: 99%

OCLN as a novel biomarker for prognosis and immune infiltrates in kidney renal clear cell carcinoma: an integrative computational and experimental characterization

Jia,

Kong,

Wang

et al. 2023

Front. Immunol.

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“…Data from the literature suggest that Wilms tumor is an immune-engaged tumor. An immune infiltrate analysis showed that CD8 and CD4 T cells were localized in a tumor and exhibited an activated phenotype [ 112 ], with the presence of activated CD8 T cells correlating with positive outcomes [ 113 ]. However, the TME may include immunosuppressive cells such as Tregs and increased plasmacytoid DCs.…”

Section: Tme Immune Profiling In Pediatric Solid Tumorsmentioning

confidence: 99%

Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy

Belgiovine,

Mebelli,

Raffaele

et al. 2024

IJMS

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Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.

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“…Immune profiling of pediatric brain tumor patient-derived orthotopic xenografts (PDOX), representing both low and high grades, consistently demonstrated the presence of B7-H3 and GD2 on tumor cell surfaces [ 66 ]. Similarly, B7-H3 has been found to be associated with poor anti-tumor immunity, therapy response, and prognosis in other pediatric tumor types such as AML, medulloblastoma, Wilms tumor, and rhabdomyosarcoma [ 67 , 68 , 69 , 70 ]. This suggests that B7-H3 may be involved in regulating the immune response within the pediatric brain tumor microenvironment.…”

Section: Influence Of the Immune Microenvironment On Pediatric Tumor ...mentioning

confidence: 99%

Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges

Pathania

2024

Cancers

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The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor’s vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment’s role in tumor development, interactions with tumor cells, and its impact on the tumor’s response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies.

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The tumor microenvironment and immune targeting therapy in pediatric renal tumors

Cited by 6 publications

References 173 publications

OCLN as a novel biomarker for prognosis and immune infiltrates in kidney renal clear cell carcinoma: an integrative computational and experimental characterization

OCLN as a novel biomarker for prognosis and immune infiltrates in kidney renal clear cell carcinoma: an integrative computational and experimental characterization

Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy

Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges

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