Butyrophilin-like 9 expression is associated with outcome in lung adenocarcinoma

Ma, Weishuang; Liang, Jiaming; Mo, Junjian; Zhang, Siyuan; Hu, Ningdong; Tian, Dan; Chen, Zisheng

doi:10.1186/s12885-021-08790-9

Cited by 12 publications

(9 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pathway analysis of hsa-miR-6514-3p revealed that it is related to the drug metabolism pathway. A study also reported that high expression of hsa-miR-6514-3p in lung adenocarcinoma tumors was associated with good prognosis [30]. In addition, our expression analysis revealed that hsa-miR-6514-3p is expressed at low levels in lung cancers.…”

Section: Discussionsupporting

confidence: 67%

miRNA Profiling of 3'UTR Variations in Sporadic Lung Carcinoma Tumours

Bagci

2023

Preprint

View full text Add to dashboard Cite

Background The aim of the study was to determine the exonic and 3'UTR sequences of EGFR, PIK3CA and KRAS genes in 39 sporadic lung cancer tumors and to reveal the relationship between the changes in the miRNA binding profile of tumors with somatic variation in the 3'UTR region and the metastatic status of the tumors. Methods The exonic and 3'UTR sequences of three genes in 39 sporadic lung carcinoma tumors were extracted by next generation sequencing. In tumors with somatic variation in the 3'UTR region, the changes caused by the variation in the miRNA binding profile were determined by bioinformatic analysis. The expression profile of miRNAs in lung cancer and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways are affected by miRNAs that differ depending on variation. Results A statistically significant correlation was found between the presence of miRNA that could not bind to the 3'UTR region due to variation in at least one of the EGFR or KRAS genes and the presence of metastasis in the tumor. It was revealed that variations in the 3'UTR regions of EGFR and KRAS oncogenes may be associated with the mechanism of metastasis and drug resistance as a result of their ability to cause increased expression of these oncogenes by preventing the binding of some miRNAs. Conclusion In this study, hsa-miR-124-3p, hsa-miR-506-3p, hsa-miR-1290 and hsa-miR-6514-3p were found to be particularly prominent in lung carcinoma in relation to these biological pathways.

show abstract

Section: Discussionsupporting

confidence: 67%

miRNA Profiling of 3'UTR Variations in Sporadic Lung Carcinoma Tumours

Bagci

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…We found these genes to be upregulated in HPV+ and cancer organoids ( Figure 3C ). Another highly upregulated gene was found to be Butyrophilin-Like Protein 9 (BTNL9) which has been implicated to be of prognostic significance in various cancer types ( 43 , 44 ). Its potential involvement in the regulation of γδ T cell mediated killing of tumour cells is unknown but deserves further investigation in light of our current findings with HPV-transformed and cancer organoids.…”

Section: Resultsmentioning

confidence: 99%

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids

Dong,

Holthaus,

Peters

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αβ T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

show abstract

“…Specifically, they proposed that tissue-specific Btnl/BTNL molecules expressed at steady state bind to an “innate” germline-encoded region on the TCR γ chain of tissue-resident γδ T cells, and that this interaction supports the maintenance of signature Vγ subsets of these cells within tissues (e.g., BTNL3/8 and Vγ4 + IEL in the human gut) but also prevents the engagement of the γδ TCR (incorporating both γ chain and δ chain) with cognate, self-encoded, complementarity-determining region 3 (CDR3)-dependent ligands induced upon tissue stress. Thus, in settings of tissue dysregulation, such as cancer, where BTNL expression is often downregulated [ 132 , 134 – 136 ], resident γδ T cells may then be released to respond to putative CDR3-dependent, stress-induced activating ligands. In support of this model, a Vγ4 + γδ TCR with defined clonal CDR3 reactivity [ 137 ] has recently been demonstrated to recognise both BTNL3 via a germline-encoded region of the γ chain, as well as the endothelial protein C receptor (EPCR) via the CDR3 [ 128 , 130 , 137 ].…”

Section: Clinical Translation: Challenges and Opportunitiesmentioning

confidence: 99%

Local γδ T cells: translating promise to practice in cancer immunotherapy

Zlatareva

2023

Br J Cancer

View full text Add to dashboard Cite

Rapid bench-to-bedside translation of basic immunology to cancer immunotherapy has revolutionised the clinical practice of oncology over the last decade. Immune checkpoint inhibitors targeting αβ T cells now offer durable remissions and even cures for some patients with hitherto treatment-refractory metastatic cancers. Unfortunately, these treatments only benefit a minority of patients and efforts to improve efficacy through combination therapies utilising αβ T cells have seen diminishing returns. Alongside αβ T cells and B cells, γδ T cells are a third lineage of adaptive lymphocytes. Less is known about these cells, and they remain relatively untested in cancer immunotherapy. Whilst preclinical evidence supports their utility, the few early-phase trials involving γδ T cells have failed to demonstrate convincing efficacy in solid cancers. Here we review recent progress in our understanding of how these cells are regulated, especially locally within tissues, and the potential for translation. In particular, we focus on the latest advances in the field of butyrophilin (BTN) and BTN-like (BTNL) regulation of γδ T cells and speculate on how these advances may address the limitations of historical approaches in utilising these cells, as well as how they may inform novel approaches in deploying these cells for cancer immunotherapy.

show abstract

Butyrophilin-like 9 expression is associated with outcome in lung adenocarcinoma

Cited by 12 publications

References 52 publications

miRNA Profiling of 3'UTR Variations in Sporadic Lung Carcinoma Tumours

miRNA Profiling of 3'UTR Variations in Sporadic Lung Carcinoma Tumours

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids

Local γδ T cells: translating promise to practice in cancer immunotherapy

Contact Info

Product

Resources

About