Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer

Morinaga, Takeshi; Iwatsuki, Masaaki; Yamashita, Kohei; Matsumoto, Chihiro; Harada, Kazuto; Kurashige, Junji; Iwagami, Shiro; Baba, Yoshifumi; Yoshida, Naoya; Komohara, Yoshihiro; Baba, Hideo

doi:10.1245/s10434-022-11665-3

Cited by 12 publications

(12 citation statements)

References 29 publications

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“…Importantly, the peptides bound to HLA-E influence NKG2A checkpoint blockade efficacy, with HLA-G peptide presentation by HLA-E on target cells associated with reduced NK mediated cytotoxicity compared with peptides derived from HLA-A/B/C [42]. Multiple solid and haematological malignancies have been observed to over-express HLA-E and associations between high HLA-E expression and worse clinical outcome have been reported in cancers including ovarian carcinoma, glioblastoma, gastric cancer and multiple myeloma [43][44][45][46].…”

Section: Expression Of Hla-e In Cancermentioning

confidence: 99%

Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer

et al. 2022

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Ligation of the inhibitory receptor NKG2A by its ligand HLA-E negatively regulates the activation of natural killer (NK) cells, as well as subsets of CD8+ T cells and innate T cell populations. NKG2A has recently become a novel immune checkpoint target for the treatment of cancer and direct antibody mediated blockade of NKG2A function is currently under assessment in two phase 3 clinical trials. In addition to direct targeting, the NKG2A:HLA-E axis can also be disrupted indirectly via multiple different targeted cancer agents that were not previously recognised to possess immunomodulatory properties. Increased understanding of immune cell modulation by targeted cancer therapies will allow for the design of rational and more efficacious drug combination strategies to improve cancer patient outcomes. In this review, we summarise and discuss the various strategies currently in development which either directly or indirectly disrupt the NKG2A:HLA-E interaction to enhance NK cell activation against cancer.

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Section: Expression Of Hla-e In Cancermentioning

confidence: 99%

Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer

et al. 2022

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“…Elevated sHLA‐E molecules are also detected in a variety of neoplastic patients 22,23 . HLA‐E is often overexpressed and associated with the worse prognosis in some solid and hematologic tumors 19–23 . It may be due to that HLA‐E molecules bind to NKG2A, an inhibitory receptor on the NK cell surface 24 ; the activation of NK cells depends on a balance between active and inhibitory receptors.…”

Section: Introductionmentioning

confidence: 99%

“…Membrane HLA‐E molecules (mHLA‐E) are ligands for the receptors on the surface of NK cells. Studies have shown that mHLA‐E molecules are highly expressed on the surface of most tumor cells 19–21 . Additionally, HLA‐E molecules also exist in the soluble isoform (sHLA‐E).…”

Section: Introductionmentioning

confidence: 99%

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Association of HLA‐E single nucleotide polymorphisms with human myeloid leukemia

Sun,

Hong,

Wang

et al. 2024

HLA

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Single nucleotide polymorphisms (SNPs) of HLA‐E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA‐E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti‐tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0.05). For myeloid leukemia, rs76971248 T was protective, while rs1264457 G was susceptible. We also found that rs76971248 affected HLA‐E mRNA transcription and membrane HLA‐E (mHLA‐E) expression in K562 cells through differently binding to transcription factor HOXA5 (p < 0.0001), while rs1264457 affected mHLA‐E expression by changing mRNA transcription and an encoding amino acid (p < 0.01). In contrast, the expression of soluble HLA‐E (sHLA‐E) was not influenced by both rs1264457 and rs76971248. The higher HLA‐E expression was detected among myeloid leukemia patients, and the K562 cells with higher HLA‐E molecules played a significant inhibitory effect on the killing activity of NK‐92MI cells (p < 0.05). In conclusion, the higher HLA‐E expression of myeloid leukemia cells is promoted by rs76971248 G and rs1264457 G, which helps escape from NK‐92MI cells' killing.

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“…[6][7][8][9] Regarding the treatment effectiveness and usefulness prognostic, BMF, HAS2, SHB, AREG, EREG and HBEGF genes are suggested as predictive markers for response to anti-HER therapies, 10 while ITGAL, HLA-E and GLP2R expression are considered as poor prognostic biomarker for GC patients. [11][12][13] Glycosylation modifications are usually associated with a poor prognosis in many cancer types. [14][15][16][17][18] In addition, the abnormal expression and activity of glycosyltransferases and glycosidase enzymes has been consistently linked to dismal prognosis in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade

et al. 2022

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Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Despite progress in the last decades, there are still no reliable biomarkers for the diagnosis of and prognosis for GC. Aberrant sialylation is a widespread critical event in the development of GC. Neuraminidases (Neu) and sialyltransferases (STs) regulate the ablation and addition of sialic acid during glycoconjugates biosynthesis, and they are a considerable source of biomarkers in various cancers. This study retrospectively characterized Neu3 and ST3Gal3 expression by immunohistochemistry in 71 paraffin-embedded GC tissue specimens and analyzed the relationship between their expression and the clinicopathological parameters. Neu3 expression was markedly increased in GC tissues compared with non-tumoral tissues (p<0.0001). Intratumoral ST3Gal3 staining was significantly associated with intestinal subtype (p=0.0042) and was negatively associated with angiolymphatic invasion (p=0.0002) and higher histological grade G3 (p=0.0066). Multivariate analysis revealed that ST3Gal3 positivity is able to predict Lauren's classification. No associations were found between Neu3 staining and clinical parameters. The in silico analysis of mRNA expression in GC validation cohorts corroborates the significant ST3Gal3 association with higher histological grade observed in our study. These findings suggest that ST3Gal3 expression may be an indicator for aggressiveness of primary GC.

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Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer

Cited by 12 publications

References 29 publications

Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer

Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer

Association of HLA‐E single nucleotide polymorphisms with human myeloid leukemia

alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade

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