Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment
BackgroundAngioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987227/full |
| _version_ | 1798029796436869120 |
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| author | Zihang Chen Qiqi Zhu Xueqin Deng Wenqing Yao Wenyan Zhang Weiping Liu Yuan Tang Sha Zhao |
| author_facet | Zihang Chen Qiqi Zhu Xueqin Deng Wenqing Yao Wenyan Zhang Weiping Liu Yuan Tang Sha Zhao |
| author_sort | Zihang Chen |
| collection | DOAJ |
| description | BackgroundAngioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-predominant AITL). However, detailed comparison of CD8-predominant AITL and common AITL are still lacking.MethodsWe compared clinicopathological features, TIL subsets, TME T cell receptor-β (TRB), and immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles in six CD8-predominant and 12 common AITLs using case-control matching (2014 to 2019).ResultsComparing with common AITLs, CD8-predominant AITLs showed more frequent edema (P = 0.011), effusion (P = 0.026), high elevated plasma EBV-DNA (P = 0.008), and shorter survival (P = 0.034). Moreover, they had more pronounced eosinophil increase (P = 0.004) and a higher Ki67 index (P = 0.041). Flow cytometry revealed an inverted CD4/CD8 ratio in TIL-Ts and lower TIL-B proportions (P = 0.041). TRB repertoire metrics deteriorated, including lower productive clones (P = 0.014) and higher clonality score (P = 0.019). The IGH repertoire was also narrowed, showing a higher proportion of the top 10 clones (P = 0.002) and lower entropy (P = 0.027). Gene expression analysis showed significant enrichment for upregulated negative regulation of immune system processes and downregulated T-cell activation and immune cell differentiation.ConclusionOur findings demonstrated that CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. These characteristics can interpret its severe clinical manifestations and poor outcomes. |
| first_indexed | 2024-04-11T19:31:09Z |
| format | Article |
| id | doaj.art-ba30cb124fd14e65b485439e6ffb347d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T19:31:09Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ba30cb124fd14e65b485439e6ffb347d2022-12-22T04:07:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.987227987227Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironmentZihang ChenQiqi ZhuXueqin DengWenqing YaoWenyan ZhangWeiping LiuYuan TangSha ZhaoBackgroundAngioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-predominant AITL). However, detailed comparison of CD8-predominant AITL and common AITL are still lacking.MethodsWe compared clinicopathological features, TIL subsets, TME T cell receptor-β (TRB), and immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles in six CD8-predominant and 12 common AITLs using case-control matching (2014 to 2019).ResultsComparing with common AITLs, CD8-predominant AITLs showed more frequent edema (P = 0.011), effusion (P = 0.026), high elevated plasma EBV-DNA (P = 0.008), and shorter survival (P = 0.034). Moreover, they had more pronounced eosinophil increase (P = 0.004) and a higher Ki67 index (P = 0.041). Flow cytometry revealed an inverted CD4/CD8 ratio in TIL-Ts and lower TIL-B proportions (P = 0.041). TRB repertoire metrics deteriorated, including lower productive clones (P = 0.014) and higher clonality score (P = 0.019). The IGH repertoire was also narrowed, showing a higher proportion of the top 10 clones (P = 0.002) and lower entropy (P = 0.027). Gene expression analysis showed significant enrichment for upregulated negative regulation of immune system processes and downregulated T-cell activation and immune cell differentiation.ConclusionOur findings demonstrated that CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. These characteristics can interpret its severe clinical manifestations and poor outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2022.987227/fullangioimmunoblastic T-cell lymphomatumor microenvironmentT cell receptor-β repertoireimmunoglobulin heavy chain repertoireTME function |
| spellingShingle | Zihang Chen Qiqi Zhu Xueqin Deng Wenqing Yao Wenyan Zhang Weiping Liu Yuan Tang Sha Zhao Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment Frontiers in Immunology angioimmunoblastic T-cell lymphoma tumor microenvironment T cell receptor-β repertoire immunoglobulin heavy chain repertoire TME function |
| title | Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment |
| title_full | Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment |
| title_fullStr | Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment |
| title_full_unstemmed | Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment |
| title_short | Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment |
| title_sort | angioimmunoblastic t cell lymphoma with predominant cd8 tumor infiltrating t cells is a distinct immune pattern with an immunosuppressive microenvironment |
| topic | angioimmunoblastic T-cell lymphoma tumor microenvironment T cell receptor-β repertoire immunoglobulin heavy chain repertoire TME function |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987227/full |
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