Analyses of the expression and prognosis of ILDR1 in human gastric cancer

Wang, Li; Zhai, Rujun; Song, Guodong

doi:10.1016/j.heliyon.2022.e10253

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…This downregulation suggests that these genes might play a role in CLL progression and pathogenesis. Indeed, several of these common genes, including EPB41L2 ( 37 ), CDK6 ( 38 ) , IL-15 ( 39 ) , ADARB1 ( 40 ), GCNT1 ( 41 ) , ILDR1 ( 42 ) , ITGA4 ( 43 ) and TSPAN3 ( 44 ), have been reported to be associated with tumor progression. Interestingly, in vitro experiments demonstrated that recombinant human BAFF upregulated EPB41L2, CDK6 and IL15 expression in CLL cells from 5 individual patients with CLL ( Supplementary Figure 5D and Supplementary Table 1 ), while the expression of the remaining genes did not change following BAFF stimulation, suggesting that BAFF does not directly regulate those tumor-promoting genes ( Supplementary Figure 5D ).…”

Section: Resultsmentioning

confidence: 99%

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia

Ullah,

Garcillán,

Whitlock

et al. 2024

Front. Immunol.

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BackgroundChronic Lymphocytic Leukemia (CLL) is characterized by the expansion of CD19+ CD5+ B cells but its origin remains debated. Mutated CLL may originate from post-germinal center B cells and unmutated CLL from CD5+ mature B cell precursors. Irrespective of precursor types, events initiating CLL remain unknown. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation remains unclear.MethodsWe generated novel CLL models lacking BAFF or APRIL. In vivo experiments were conducted to explore the impact of BAFF or APRIL loss on leukemia initiation, progression, and dissemination. Additionally, RNA-seq and quantitative real-time PCR were performed to unveil the transcriptomic signature influenced by BAFF in CLL. The direct role of BAFF in controlling the expression of tumor-promoting genes was further assessed in patient-derived primary CLL cells ex-vivo.ResultsOur findings demonstrate a crucial role for BAFF, but not APRIL, in the initiation and dissemination of CLL cells. In the absence of BAFF or its receptor BAFF-R, the TCL1 transgene only increases CLL cell numbers in the peritoneal cavity, without dissemination into the periphery. While BAFF binding to BAFF-R is dispensable for peritoneal CLL cell survival, it is necessary to activate a tumor-promoting gene program, potentially linked to CLL initiation and progression. This direct role of BAFF in controlling the expression of tumor-promoting genes was confirmed in patient-derived primary CLL cells ex-vivo.ConclusionsOur study, involving both mouse and human CLL cells, suggests that BAFF might initiate CLL through mechanisms independent of cell survival. Combining current CLL therapies with BAFF inhibition could offer a dual benefit by reducing peripheral tumor burden and suppressing transformed CLL cell output.

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Section: Resultsmentioning

confidence: 99%

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia

Ullah,

Garcillán,

Whitlock

et al. 2024

Front. Immunol.

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BAFF, but not APRIL, initiates Chronic Lymphocytic Leukemia by inducing tumor-promoting genes rather than cell survival.

Ullah

Garcillán

Whitlock

et al. 2023

Preprint

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Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults, characterized by the expansion of CD19+ CD5+ B cells. The origin of CLL remains debated, with one model suggesting that CLL cells carrying mutations in the variable regions of immunoglobulin are derived from post-germinal center B cells, whereas unmutated CLL cells originate from CD5+ mature B cell precursors. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation is unclear. Using the TCL1-transgenic (Tg) model, we have demonstrated that BAFF, but not, APRIL is needed for the initiation and dissemination of CLL. In the absence of BAFF or its receptor BAFF-R, expression of the TCL1 transgene increases CLL cell numbers in the peritoneal cavity but does not allow dissemination into the periphery. BAFF binding to BAFF-R is not required for the survival of peritoneal CLL cells but for the expression of tumor-promoting genes, likely allowing peritoneal CLL cells to disseminate to other sites to drive CLL. Our findings unveil BAFF as an unrecognized tumor-promoting cytokine in CLL. Combining current CLL therapies with BAFF inhibition may offer dual benefits: reducing peripheral tumor burden and suppressing transformed CLL cell output.

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Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease

Yeyeodu,

Hanafi,

Webb

et al. 2024

Front. Endocrinol.

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Both cancer and cardio-metabolic disease disparities exist among specific populations in the US. For example, African Americans experience the highest rates of breast and prostate cancer mortality and the highest incidence of obesity. Native and Hispanic Americans experience the highest rates of liver cancer mortality. At the same time, Pacific Islanders have the highest death rate attributed to type 2 diabetes (T2D), and Asian Americans experience the highest incidence of non-alcoholic fatty liver disease (NAFLD) and cancers induced by infectious agents. Notably, the pathologic progression of both cancer and cardio-metabolic diseases involves innate immunity and mechanisms of inflammation. Innate immunity in individuals is established through genetic inheritance and external stimuli to respond to environmental threats and stresses such as pathogen exposure. Further, individual genomes contain characteristic genetic markers associated with one or more geographic ancestries (ethnic groups), including protective innate immune genetic programming optimized for survival in their corresponding ancestral environment(s). This perspective explores evidence related to our working hypothesis that genetic variations in innate immune genes, particularly those that are commonly found but unevenly distributed between populations, are associated with disparities between populations in both cancer and cardio-metabolic diseases. Identifying conventional and unconventional innate immune genes that fit this profile may provide critical insights into the underlying mechanisms that connect these two families of complex diseases and offer novel targets for precision-based treatment of cancer and/or cardio-metabolic disease.

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Analyses of the expression and prognosis of ILDR1 in human gastric cancer

Cited by 3 publications

References 36 publications

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia

BAFF, but not APRIL, initiates Chronic Lymphocytic Leukemia by inducing tumor-promoting genes rather than cell survival.

Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease

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