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NKT cells contribute to alleviating lung metastases in adenoid cystic carcinoma

ABSTRACT: Through CD4 and CD8 immunohistochemical analysis, we systematically established immune desert, exclusion, and inflammatory types in SACC primary lesions and lung metastases. Notably, the majority of lung metastases exhibited immune inflammatory types in contrast to the common desert type in primary SACC tissue. Tissue type rather than MYB-NFIB fusion should be a key factor causing differences in the immune environment. At the single-cell level, we demonstrated the presence of a small amount of anergy T cell types and a few elevated cytokines in the primary inflammatory tissues without MYB-NFIB fusion; and a large amount of myeloid-derived suppressor cells (MDSCs), a small amount of activated CD8+ NKT-like cells and substantially elevated cytokines in the primary exclusion tissues with MYB-NFIB fusion. In contrast, in the inflammatory metastatic lung tissues without MYB-NFIB fusion, small numbers of memory CD4+ and CD8+ cells were presented, but anergy CD8+ NKT-like cells and only CCL28 were elevated. Moreover, validated by immunodeficient nude mice, NKT cells are the remarkable effector cells in reducing lung metastasis, but required advance activation by a low invasive SACC cell line with higher human leukocyte antigen (HLA)-A, -B, and C expression induction.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217603 | GEO | 2025/10/29

REPOSITORIES: GEO

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Project description:Activation of peripheral T lymphocytes in the absence of pathogen induced inflammation or costimulatory signals results in tolerance. Two different tolerance mechanisms have been described, deletion and anergy. We recently demonstrated that an important variable which is responsible for the decision between anergy and deletion for CD8 T cells is the strength of signaling through the T cell receptor(Redmond and Sherman, Immunity 22:275,2005). However, it is not know what the downstream signals are that result in death(deletion) vs. survival(anergy)of the activated cells. Marth and co-workers have previously shown that CD8 T cell apoptosis under conditions similar to those that occur during tolerance in vivo may involve a change in protein glycosylation (Van Dyken et.al., Mol.Cell.Bio.27:1096,2007).In order to assess the role of protein glycosylation in the decision between deletion vs. anergy in immune tolerance, we have prepared purified TCR transgenic CD8 T cells stimulated in vivo using a strong antigenic signal (anergy conditions) or a weak antigenic signal (deletion conditions) with cognate antigen. We wish to assess transcriptional differences in genes involved in protein glycosylation in these 2 cell populations. The control population will be naive trangenic CD8 cells. Dr. Sherman's lab aims to assess the role of protein glycosylation in the decision between deletion vs. anergy in immune tolerance, they have prepared purified TCR transgenic CD8 T cells stimulated in vivo using a strong antigenic signal (anergy conditions) or a weak antigenic signal (deletion conditions) with cognate antigen. Dr. Sherman's lab wishes to assess transcriptional differences in genes involved in protein glycosylation in these 2 cell populations. Then control population will be naïve transgenic CD8 cells. RNA preparations of mouse CD8 T cells from the B10D2 strain with three different conditions (Naïve, Deleted, and Anergic) were sent to the Microarray Core (E). The RNA was amplified, labeled, and hybridized to the GLYCOv4 microarrays.

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NKT cells contribute to alleviating lung metastases in adenoid cystic carcinoma

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