High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer
| العنوان: | High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer |
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| المؤلفون: | Natasha Di Costanzo, Catherine Mitchell, Le Ying, Laura K. Mackay, Feng Yan, Rita A. Busuttil, Daniela Gm Tantalo, Heloise Halse, Minyu Wang, Han Xian Aw Yeang, Yu Sun, Ian Gordon, Dakang Xu, Paul J Neeson, Yu-Kuan Huang, Alex Boussioutas, Joseph Ch Kong |
| المصدر: | Clinical & Translational Immunology Clinical & Translational Immunology, Vol 9, Iss 5, Pp n/a-n/a (2020) |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | lcsh:Immunologic diseases. Allergy, 0301 basic medicine, T cell, medicine.medical_treatment, Immunology, Biology, CD8+ T cells, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, Cytotoxic T cell, General Nursing, gastric cancer, FOXP3, Immunotherapy, Gene signature, Immune checkpoint, CD4+FOXP3+ T cells, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Original Article, lcsh:RC581-607, CD8, interferon‐gamma gene signature |
| الوصف: | Objectives To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed. Methods The association of GC patients’ outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts. Results Increased CD4+FOXP3+ T‐cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4+FOXP3+ T cells had a close interaction with CD8+ T cells rather than tumor cells. High densities of CD4+FOXP3+ T cells and CD8+ T cells (High‐High) independently predicted prolonged patient survival. Furthermore, the interferon‐gamma (IFN‐γ) gene signature and PDL1 expression were up‐regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High‐High group also had excellent survival. The High‐High GS/CIN tumors were coupled with increased frequencies of Tbet+CD4+ T cells and central memory CD4+ T cells in the peripheral blood. Conclusion These novel findings identify the combination of CD8+ T cells and FOXP3+CD4+ T cells as a significant prognostic marker for GC patients, which also could potentially be targeted and applied in the combination therapy with immune checkpoint blockades in precision medicine. In this work, we show an increased CD4+FOXP3+ T cell density in the tumour core correlated with prolonged survival and CD4+FOXP3+ T cells clustered with CD8+ T cells rather than tumour cells. High density of CD4+FOXP3+ T cells and CD8+ T cells (High‐High) independently predicted prolonged patient survival. These High‐High tumours were coupled with an increased IFN‐γ response, antigen presentation, DCs differentiation and PDL1 upregulation in the local tumours, as well as enrichment of Tbet+ CD4+ T cells and central memory CD4+ T cells circulating in the peripheral blood. |
| تدمد: | 2050-0068 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e32e258c6a8fa1c0d9f7db674a64724Test https://doi.org/10.1002/cti2.1127Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3e32e258c6a8fa1c0d9f7db674a64724 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20500068 |
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