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1.
Cell ; 184(2): 404-421.e16, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33357445

RESUMO

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Análise de Célula Única , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Regulação Neoplásica da Expressão Gênica , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Células Mieloides/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Fenótipo , RNA-Seq , Microambiente Tumoral
2.
Clin Transl Med ; 11(1): e253, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33463049

RESUMO

The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA+ IGLC2+ plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8+ cycling B cells/CCR5+ T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.


Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/fisiopatologia , Transdução de Sinais/fisiologia , Microambiente Tumoral/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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