RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases.
Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases.
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IV 期结直肠癌预后较差,肝转移即使切除后仍容易复发。本研究旨在通过免疫组织化学染色鉴定常见癌症抗原,作为结直肠癌抗原特异性免疫治疗的潜在靶点。研究分析了原发灶和肝转移灶 85 份手术标本中 7 种常见癌抗原(CLDN1、EphB4、LAT1、FOXM1、HSP105、ROBO1、SPARC)的表达水平和细胞内定位,以及 HLA I 类分子表达;根据染色强度和阳性染色评分评估抗原表达。在 25 例原发灶中,7 种癌抗原分别在 88%–96% 病例中表达,HLA I 类分子在 80.0% 病例的细胞膜上表达。在 60 例肝转移灶中,FOXM1 和 SPARC 的表达约为原发灶的一半;其他抗原和 HLA I 类分子在两类病灶中均高表达。多数原发灶和肝转移灶患者可能适合接受靶向 CLDN1、EphB4 和 LAT1 的 CAR-T。HLA I 类分子高表达病例可能适合疫苗疗法和 TCR-T,靶向原发灶中的 CLDN1、EphB4、LAT1、FOXM1、HSP105、ROBO1 和 SPARC;而肝转移灶可靶向上述抗原,但不包括 FOXM1 和 SPARC。
Stage IV colorectal cancer has a poor prognosis, and liver metastases are prone to recurrence, even after resection.
This study aimed to identify common cancer antigens, using immunohistochemical staining, as promising targets for antigen-specific immunotherapies in colorectal cancer.
We analyzed expression levels and intracellular localization of seven common cancer antigens, CLDN1, EphB4, LAT1, FOXM1, HSP105 , ROBO1, and SPARC, and human leukocyte antigen (HLA) class I via immunohistochemical staining of 85 surgical specimens from primaries and liver metastases. Staining intensity and positive staining were scored to evaluate antigen expression. In 25 primaries, seven cancer antigens were expressed in 88-96% of cases, while HLA class I was expressed on the cell membrane in 80. 0% of cases.
In 60 liver metastases, FOXM1 and SPARC expression were approximately half that observed in the primaries. Other antigens and HLA class I were highly expressed in both. Most of the primaries and liver metastases may benefit from chimeric antigen receptor-T cell therapy targeting CLDN1, EphB4, and LAT1.
Cases with high HLA class I expression may be suitable for vaccine-based and T cell receptor-T cell therapy targeting CLDN1, EphB4, LAT1, FOXM1, HSP105 , ROBO1, and SPARC for primaries and targeting antigens, excluding FOXM1 and SPARC, for liver metastases.
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