Dataset Information

Tertiary lymphoid structure and decreased CD8⁺ T cell infiltration in minimally invasive adenocarcinoma.

ABSTRACT: Knowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4⁺ T cell infiltration, high B-cell activation, and low CD8⁺ T cell infiltration. The high expression of markers for B cells, activated CD4⁺ T cells, and follicular helper T (Tfh) cells in bulk MIA samples and three independent single-cell RNA-seq datasets implied tertiary lymphoid structures (TLS) formation. Multiplex immunohistochemistry staining validated TLS formation and revealed an enrichment of follicular regulatory T cells (Tfr) in TLS follicles, which may explain the lower CD8⁺ T cell infiltration and attenuated anti-tumor immunity in MIA. Our study demonstrates how integrating transcriptome and pathology characterize TME and elucidate potential mechanisms of tumor immune evasion.

SUBMITTER: Wang J

PROVIDER: S-EPMC8873609 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tertiary lymphoid structure and decreased CD8+ T cell infiltration in minimally invasive adenocarcinoma.

Wang Jin J Jiang Dongbo D Zheng Xiaoqi X Li Wang W Zhao Tian T Wang Di D Yu Huansha H Sun Dongqing D Li Ziyi Z Zhang Jian J Zhang Zhe Z Hou Likun L Jiang Gening G Fei Ke K Zhang Fan F Yang Kun K Zhang Peng P

iScience 20220209 3

Knowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4+ T cell infiltration, high B-cell activation, and low CD8+ T cell infi ...[more]

PMID: 35243243

Similar Datasets

Project description:ObjectivesThe aim of this study was to determine the status of tertiary lymphoid structures (TLSs) using radiomic features in patients with invasive pulmonary adenocarcinoma (IA).MethodsIn this retrospective study, patients with IA from November 2015 to March 2024 were recruited from two independent centers (center 1, training and internal test data set; center 2, external test data set). TLS was divided into two groups according to hematoxylin-eosin staining. Radiomic features were extracted, and support vector machine (SVM) were implemented to predict the status of TLSs. Receiver operating characteristic (ROC) curves were used to analyze diagnostic performance. Furthermore, visual assessments of the test set were also conducted by two thoracic radiologists and compared with the radiomics results.ResultsA total of 456 patients were included (training data set, n = 278; internal test data set, n = 115; external test data set, n = 63). The area under the curve (AUC) of the radiomics model on the validation set, the internal test set, and the external test set were 0.781 (95% confidence interval (CI): 0.659-0.905;), 0.804 (95% CI: 0.723-0.884;) and 0.747 (95% CI: 0.621-0.874;), respectively. In the visual assessments, the mean CT value and air bronchogram were important indicators of TLS, the AUC was 0.683. In the external test set, the AUC of the clinical model was 0.632.ConclusionsThe radiomics model has a higher AUC than the clinical model and effectively discriminates TLSs in patients with IA.Critical relevance statementThis study demonstrates that the radiomics-based model can differentiate TLSs in patients with IA. As a non-invasive biomarker, it enhances our understanding of tumor prognosis and management.Key pointsTLSs are closely related to favorable clinical outcomes in non-small cell lung cancer. Radiomics from Chest CT predicted TLSs in patients with IA. This study supports individualized clinical decision-making for patients with IA.

Project description:Surgical trauma of biomaterial implantation significantly influences the immune system and the biological effects of biomaterials. Minimally invasive surgery has become a trend of clinical development but violating the concept of osteoimmunomodulation will hinder the biological effects of materials. Our study focused on biphasic calcium phosphate (BCP), the ectopia osteoinductive materials, filling the research blank of the significance of adaptive immunity crosstalk with bone biomaterials, and improving the interaction mechanism between bone biomaterials and immune response. Methods: The BCP bioceramics were implanted by conventional and minimally invasive methods in the gastrocnemius wild-type or T cells depleted mice to test the effect of ectopia osteoinduction. Moreover, flow cytometry was used to detect immune responses, T cell sorting and Western Blot molecular biology experiments, and transwell assays migration of mesenchymal stem cells (MSCs). Results: We found that BCP, an implantable osteoinductive material, could not activate the adaptive immune response mediated by T cells after minimally invasive surgery. Further studies revealed that under the conventional non-minimally invasive BCP implantation, a positive correlation existed between T cell recruitment and the infiltration and osteogenic differentiation of MSCs. Interestingly, after BCP was implanted by minimally invasive surgery or implanted in T cell depleted mice, MSCs infiltration and osteogenic differentiation were significantly reduced, and BCP could not achieve the biological effects of ectopia ossification. Finally, we confirmed that a certain extent inflammatory stimulation activated the adaptive immune response mediated by T cells, up-regulated the nuclear factor-κB (NF-κB) signal in T cells, released a large amount of chemokine C-C motif chemokine ligand 5(CCL5) to recruit MSCs to the surrounding material, and finally achieved the ideal effect of osteoinduction. Conclusion: From experimental research and clinical surgery, this study discovered that the T cells are indispensable in the ectopia ossification mediated by osteoinductive materials, put forward and confirmed the surgery method as a key variable factor restricting the application effect of biological materials, enriched the key mechanism of adaptive immunity in osteoimmunomodulation, and laid a theoretical foundation for the development of osteoinductive materials and bone tissue regeneration.

Dataset Information

Tertiary lymphoid structure and decreased CD8⁺ T cell infiltration in minimally invasive adenocarcinoma.

Publications

Tertiary lymphoid structure and decreased CD8<sup>+</sup> T cell infiltration in minimally invasive adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets