Targeting the Myeloid-Derived Suppressor Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best Limited to Specific Subtypes of Gastric Cancers

Kodach, Liudmila L.; Peppelenbosch, Maikel P.

doi:10.1053/j.gastro.2021.03.047

Cited by 12 publications

(5 citation statements)

References 5 publications

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“…Some have suggested that variation in myeloid cells subsets may be associated with different patient outcomes 35, 36 . From our vantage point, studies of the tumor microenvironment only provide information concerning the relative abundance or scarcity of myeloid cells.…”

Section: Resultsmentioning

confidence: 99%

JAMMIT Analysis Defines 2 Semi-Independent Immune Processes Common to 29 Solid Tumors

Zitello

Vo²,

Bowler

et al. 2021

Preprint

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Immunophenotype of solid tumors has relevance to cancer immunotherapy, as not all patients respond optimally to treatment utilizing monoclonal antibodies. Bioinformatic studies have failed to clearly identify tumor immunophenotype in a way that encompasses a wide variety of tumor types and highlights fundamental differences among them, complicating prediction of patient clinical response. The novel JAMMIT algorithm was used to analyze mRNA data for 33 cancer types in The Cancer Genome Atlas (TCGA). We found that B cells and T cells constitute the principal source of variation in most patient cohorts, and that virtually all solid malignancies formed three hierarchical clustering patterns with similar molecular features. The second main source of variability in transcriptomic studies we attribute to monocytes. We identified the three tumor types as TC1-mediated, TC17-mediated and nonimmunogenic immunophenotypes and used a 3-gene signature to approximate infiltration by agranulocytes. Methods of in silico validation such as pathway analysis, Cibersort and published data from treated cohorts were used to substantiate these findings. Monocytic infiltrate is found to be related to patient survival according to immunophenotype, important differences in some solid tumors are identified and deficiencies of common bioinformatic approaches relevant to diagnosis are detailed by this work.

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Section: Resultsmentioning

confidence: 99%

JAMMIT Analysis Defines 2 Semi-Independent Immune Processes Common to 29 Solid Tumors

Zitello

Vo²,

Bowler

et al. 2021

Preprint

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“…A previous study indicated that the patients' different responses to medicine were due to different subtypes [ 36 ]. Therefore, we are trying to explore potential treatments by mining molecular mechanisms.…”

Section: Discussionmentioning

confidence: 99%

A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients

Wang

Liu

et al. 2023

BMC Nephrol

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Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-β (TGF-β) pathways. In recent years, increasing evidence has revealed the pivotal role of ubiquitination in tumorigenesis of KIRC. However, USPs' molecular mechanism and clinical relevance in kidney cancer still need further exploration. Our study first determined prognosis-related ubiquitin-specific proteases (PRUSPs) in KIRC. We found these genes co-expressed with each other and might regulate different substrates. Based on the USPs' expression, the PRUSPs risk signature was constructed to predict the survival probability of KIRC patients. The patients in high-PRUSPs-risk group showed a low survival rate. ROC and calibration curve indicated a discriminate capacity of the signature, and uni-/multi-variate Cox regression analysis revealed that the PRUSPs score is an independent prognostic factor. In different KIRC clinical subgroups and external validation cohorts (including E-MTAB-1980 and TCGA-KIRP cohorts), the PRUSPs risk signature showed strong robustness and practicability. Further analysis found that high-risk group showed activation of immune-related pathways and high PD-1/CTLA4 expression, revealing that high-risk patients might be sensitive to immunotherapy. In summary, we constructed the USPs risk signature to predict kidney cancer prognosis, which provided the theoretical foundation for further clinical or pre-clinical experiments.

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“… 32 FTO is also known to be related to tumor immune infiltration observed in various cancers. 33 With immunotherapy attracting extensive attention for treating multiple cancers, including advanced GC, 34 genetic variants may potentially serve as novel biomarkers for predicting immunological response. ALKBH1 has been reported to be up-regulated in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms of m6A Erasers FTO and ALKBH1 Associated with Susceptibility to Gastric Cancer

Li¹,

Zhou²,

Liu³

et al. 2022

PGPM

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Purpose Fat mass and obesity-associated protein (FTO) and AlkB homolog 1 (ALKBH1) are m6A demethylases that have been demonstrated to be associated with the overall survival of patients with gastric cancer (GC). This study investigates the influence of genetic variants of FTO and ALKBH1 on susceptibility to GC. Patients and Methods Potentially functional single nucleotide polymorphisms (SNPs) of FTO and ALKBH1 were genotyped in 419 patients with GC and 569 healthy controls by Kompetitive allele-specific PCR. Results The AG and AG/AA variants of FTO rs2287142 were significantly associated with a decreased GC risk (for AG/AA vs GG: adjusted OR = 0.73, p = 0.020). The GA and GA/GG variants of ALKBH1 rs1076496 were closely correlated with an increased risk of GC in people aged ≥ 55 years (for GA/GG vs AA: adjusted OR = 1.51, p = 0.041) but showed a decreasing tendency of risk of GC in people aged <55 years (adjusted OR = 0.85, p = 0.444). FTO rs2287142 and ALKBH1 rs1076496 conformed to the principle of a dominant model. FTO haplotype rs1421091-rs1421092-rs2287142-rs9939609 CTAT was closely associated with a lower risk of total GC (adjusted OR = 0.62, p = 0.023), while CTGA was linked with an increased risk of intestinal GC (adjusted OR = 2.51, p = 0.005). ALKBH1 rs1048147-rs1076496-rs11159286 CAC haplotype was significantly associated with a decreased risk of GC in people aged ≥ 55 years (adjusted OR = 0.41, p = 0.008). The FTO rs2287142-rs9939609 AG/AA-TT combination was associated with a decreased risk of GC only in the presence of rs1421091 TC/TT (adjusted OR = 0.70, p = 0.047), demonstrating that these FTO SNPs might have a cooperative effect on susceptibility to GC. Conclusion FTO and ALKBH1 SNPs may have predictive value in evaluating susceptibility to GC with differing age or Lauren classification.

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Targeting the Myeloid-Derived Suppressor Cell Compartment for Inducing Responsiveness to Immune Checkpoint Blockade Is Best Limited to Specific Subtypes of Gastric Cancers

Cited by 12 publications

References 5 publications

JAMMIT Analysis Defines 2 Semi-Independent Immune Processes Common to 29 Solid Tumors

JAMMIT Analysis Defines 2 Semi-Independent Immune Processes Common to 29 Solid Tumors

A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients

Gene Polymorphisms of m6A Erasers FTO and ALKBH1 Associated with Susceptibility to Gastric Cancer

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