Immune organoids: from tumor modeling to precision oncology

Dao, Vinh; Yuki, Kanako; Lo, Yuan–Hung; Nakano, Michitaka; Kuo, Calvin J.

doi:10.1016/j.trecan.2022.06.001

Cited by 23 publications

(14 citation statements)

References 80 publications

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“…To uncover the potential role of CREB3L1 in modulating the tumor immune microenvironment, we firstly confirmed that CREB3L1 expression levels were positively related to immune scores and stroma scores in multiple human cancers by utilizing ESTIMATE. The crosstalk between cancer cells and immune cells has been found to contribute to the microenvironment which facilitates tumor growth and metastasis, and immune cells presenting in the tumor microenvironment play a determinative role in cancer survival and development ( Hinshaw and Shevde, 2019 ; Marzagalli et al, 2019 ; Dao et al, 2022 ). Hence, we further explored the correlation between CREB3L1 expression levels and the abundance of infiltrating immune cells in pan-cancer.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy

Lin

Xiao

et al. 2022

Front. Genet.

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Background: CAMP response element binding protein 3-like 1 (CREB3L1) has been indicated as a critical biomarker and can modulate multifaced behaviors of tumor cells in diverse cancers. However, a systematic assessment of CREB3L1 in pan-cancer is of absence, and the predictive value of CREB3L1 in cancer prognosis, the tumor immune microenvironment and the efficacy of immunotherapy remains unexplored.Methods: CREB3L1 expression in 33 different cancer types was investigated using RNAseq data from The Cancer Genome Atlas (TCGA) database. The characteristics of CREB3L1 alternations were illustrated in cBioPortal database. The prognostic and clinicopathological value of CREB3L1 was analyzed through clinical data downloaded from the TCGA database. The potential role of CREB3L1 in the tumor immune microenvironment was illustrated by utilizing CIBERSORT and ESTIMATE algorithms, and TISIDB online database. The associations between CREB3L1 expression and tumor mutation burden (TMB), and microsatellite instability (MSI) were assessed by spearman’s rank correlation coefficient. Furthermore, Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential biological functions and downstream pathways of CREB3L1 in different human cancers. The correlations of CREB3L1 expression with PD-1/PD-L1 inhibitors efficacy and drug sensitivity were also investigated.Results: The expression of CREB3L1 was abnormally high or low in several different cancer types, and was also strictly associated with the prognosis of cancer patients. CREB3L1 expression levels have a strong relationship with infiltrating immune cells, including regulatory T cells, CD8+ T cells, macrophages, B naïve cells, dendritic cells and mast cells. CREB3L1 expression was also correlated with the expression of multiple immune-related biomolecules, TMB, and MSI in several cancers. Moreover, CREB3L1 had promising applications in predicting the immunotherapeutic benefits and drug sensitivity in cancer management.Conclusions: Our results highlight the value of CREB3L1 as a predictive biomarker for the prognosis and immunotherapy efficacy in multiple cancers, and CREB3L1 seems to play key roles in the tumor immune microenvironment, suggesting the role of CREB3L1 as a promising biomarker for predicting the prognosis and immune-related signatures in diverse cancers.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy

Lin

Xiao

et al. 2022

Front. Genet.

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“…For instance, at present, the efficacy determination of the inhibitors of immune checkpoints programmed death-1/programmed death ligand-1 (PD-1/PD-L1) using PDOs model cannot be conclusive and need further research attention [ 231 ]. Recently, there have been efforts to create a native immune microenvironment within PDOs by co-culturing of more complex immune and stromal components in a more compartmentalized manner [ 232 , 233 ].…”

Section: Models To Study Interactions Of the Tmementioning

confidence: 99%

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

2022

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Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME’s individual components and their interplay at higher resolution. Deeper understanding of the immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a possibility of reprogramming of TME components to overcome the widely prevailing issue of immunotherapeutic resistance. The focus of the present review is to understand the complexity of TME and comprehending future perspective of its components as potential therapeutic targets. The later part of the review describes the sophisticated 3D models emerging as valuable means to study TME components and an extensive account of advanced bioinformatic tools to profile TME components and predict neoantigens. Overall, this review provides a comprehensive account of the current knowledge available to target TME.

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“…In addition, autologous peripheral blood mononuclear cells (PBMCs) or tumor-infiltrating lymphocytes (TILs) have been used in vitro to facilitate tumor recognition and high cytotoxic activity through coculture with certain tumor organoids, as demonstrated in breast and colorectal cancer organoids (20)(21)(22). These coculture systems, which model tumor-immune cell interactions, are essential and convenient for preclinical evaluation of anti-PD-1/PD-L1 or related immunotherapy combination strategies in vitro (23). However, there is a paucity of melanoma organoid models reported or well characterized, particularly for the rare oral MM (OMM) (24).…”

Section: Introductionmentioning

confidence: 99%

A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options

Sun,

Kang,

et al. 2023

Sci. Adv.

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Mucosal melanoma (MM), an aggressive rare subtype of melanoma, is distinct from cutaneous melanoma and has poor prognoses. We addressed the lack of cell models for MM by establishing 30 organoids of human oral MM (OMM), which retained major histopathological and functional features of parental tumors. Organoid groups derived from chronologically or intratumorally distinct lesions within the same individual displayed heterogeneous genetics, expression profiles, and drug responses, indicating rapid tumor evolution and poor clinical response. Furthermore, transcriptome analysis revealed receptor tyrosine kinases (RTKs) signaling, particularly NGFR , a nerve growth factor receptor, was significantly up-regulated in OMMs and organoids from patients resistant to anti–programmed cell death protein 1 (anti–PD-1) therapy. Combining anti–PD-1 with anlotinib (a phase 2 multitarget RTK inhibitor for OMM) or NGFR knockdown enhanced the effective activity of immune cells in organoid–immune cell coculture systems. Together, our study suggested that OMM organoids serve as faithful models for exploring tumor evolution and immunotherapy combination strategies.

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Immune organoids: from tumor modeling to precision oncology

Cited by 23 publications

References 80 publications

Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy

Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options

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