| 项目编号 |
PRJCA007578 |
| 项目标题 |
Sirpa restrains antitumor immunity by modulating the tumor immune microenvironment |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
|
| 物种名称 |
Mus musculus
Homo sapiens
|
| 描述信息 |
Immunosuppressive myeloid cells in the tumor immune microenvironment (TIME) constrain T cell activity and hinder immunotherapeutic efficacy, but the precise mechanisms remain undefined. Here, by performing single-cell RNA sequencing (scRNA-seq) of tumor-infiltrating immune cells (TIICs) from colorectal cancer (CRC) patients, we found that macrophages and granulocytic myeloid-derived suppressor cells (gMDSCs) displaying the highest immune-inhibitory signatures were the most increased immunocytes in tumors compared to corresponding normal tissue. Tumor-infiltrating myeloid cells exhibited significantly increased expression of ITIM-bearing receptors such as SIRPA, CLEC4A and SIGLEC9. Intriguingly, Sirpa-/- mice but not Clec4a2-/- or Siglece-/- mice were more resistant to tumor progression than wild-type (WT) mice. Additionally, the SIRPA expression level was inversely correlated with patient survival and cancer recurrence. Sirpa deficiency was associated with decreased total myeloid cells in TIICs, in parallel with expansion of the TAM_Ccl8hi and gMDSC_H2-Q10hi subsets, which showed strong antitumor activity and cell-cell communication and thus facilitated the consequent infiltration and proliferation of T cells in tumors. Interestingly, anti-PD-L1 immunotherapy exhibited superior efficacy in Sirpa-/- mice. Therefore, these findings suggest that Sirpa deletion enhances innate and adaptive immune activation in the TIME; thus, Sirpa blockade could be a promising strategy to improve cancer immunotherapy. |
| 样品范围 |
Single cell |
| 发布日期 |
2023-09-25 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 38200243
|
Sirpα on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47
|
Nature Cancer
|
10.1038/s43018-023-00691-z
|
2024
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Key R&D Program of China
|
Basic Research Grant
|
2021YFF1200900
|
|
|
|
| 提交者 |
Wenfei
Jin (jinwf@sustech.edu.cn)
|
| 提交单位 |
Southern University of Science and Technology |
| 提交日期 |
2021-12-14 |
