在 HLA II 类阴性结直肠癌中呈现 CD4+ T 细胞监测的 HLA II 类新抗原。

IF 6.5 2区 医学 Q1 IMMUNOLOGY Oncoimmunology Pub Date : 2024-12-31 Epub Date: 2024-09-19 DOI:10.1080/2162402X.2024.2404665
Satoru Matsumoto, Takahiro Tsujikawa, Serina Tokita, Mai Mohamed Bedeir, Kazuhiko Matsuo, Fumitake Hata, Yoshihiko Hirohashi, Takayuki Kanaseki, Toshihiko Torigoe
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引用次数: 0

摘要

新抗原反应性 CD4+ T 细胞在抗肿瘤免疫反应中发挥着关键作用。然而,大多数上皮肿瘤的 HLA II 类(HLA-II)表面表达阴性,而且人们对 HLA-II 抗原的加工过程知之甚少。在这里,我们采用蛋白质基因组学方法直接鉴定了 HLA-II 阴性结直肠癌(CRC)组织中自然呈现的 HLA-II 新抗原。这些新抗原具有免疫原性,能诱导患者CD4+ T细胞产生Th1记忆表型,从而产生IFN-γ、IL2和TNF-α。多重免疫组化(IHC)显示,Th 细胞与 HLA-II 阳性的抗原递呈细胞(APCs)在浸润边缘和三级淋巴结构(TLS)内相互作用。在我们的 CRC 队列中,基质 APC 的密度与肿瘤微环境 (TME) 中的 HLA-II 抗原呈递相关,而 TLS 的数量与肿瘤中的体细胞突变数量呈正相关。这些结果表明在HLA-II阴性的CRC中存在新抗原特异性CD4+监测,并提示巨噬细胞和树突状细胞(DC)在侵袭边缘和TLS的抗原呈递中可能发挥作用。TME中的基质APC有可能被用作HLA-II新抗原识别的来源。
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HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer.

Neoantigen-reactive CD4+ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4+ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4+ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.

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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
期刊最新文献
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