PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow
Despite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site,...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-08-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.686156/full |
| _version_ | 1818433642417881088 |
|---|---|
| author | Ling Xu Ling Xu Lian Liu Danlin Yao Xiangbo Zeng Yikai Zhang Yikai Zhang Jing Lai Jun Zhong Xianfeng Zha Runhui Zheng Yuhong Lu Minming Li Zhenyi Jin Sudheendra Hebbar Subramanyam Shaohua Chen Xin Huang Yangqiu Li Yangqiu Li |
| author_facet | Ling Xu Ling Xu Lian Liu Danlin Yao Xiangbo Zeng Yikai Zhang Yikai Zhang Jing Lai Jun Zhong Xianfeng Zha Runhui Zheng Yuhong Lu Minming Li Zhenyi Jin Sudheendra Hebbar Subramanyam Shaohua Chen Xin Huang Yangqiu Li Yangqiu Li |
| author_sort | Ling Xu |
| collection | DOAJ |
| description | Despite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site, and peripheral blood (PB) and understanding how T cells are affected by AML induction chemotherapy or the influence of age may help to select patients who may benefit from ICI treatment. In this study, we comprehensively compared the distribution of PD-1 and TIGIT, two of the most well-studied IC proteins, in PB and BM T cells from AML patients at the stages of initial diagnosis, complete remission (CR), and relapse-refractory (R/R) disease after chemotherapy. Our results show that PD-1 was generally expressed higher in PB and BM T cells from de novo (DN) and R/R patients, while it was partially recovered in CR patients. The expression of TIGIT was increased in the BM of CD8+ T cells from DN and R/R patients, but it did not recover with CR. In addition, according to age correlation analysis, we found that elderly AML patients possess an even higher percentage of PD-1 and TIGIT single-positive CD8+ T cells in PB and BM, which indicate greater impairment of T cell function in elderly patients. In addition, we found that both DN and R/R patients accumulate a higher frequency of PD-1+ and TIGIT+ CD8+ T cells in BM than in corresponding PB, indicating that a more immunosuppressive microenvironment in leukemia BM may promote disease progression. Collectively, our study may help guide the combined use of anti-PD-1 and anti-TIGIT antibodies for treating elderly AML patients and pave the way for the exploration of strategies for reviving the immunosuppressive BM microenvironment to improve the survival of AML patients. |
| first_indexed | 2024-12-14T16:24:20Z |
| format | Article |
| id | doaj.art-0530309469c6485484285932f806bf03 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T16:24:20Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0530309469c6485484285932f806bf032022-12-21T22:54:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.686156686156PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone MarrowLing Xu0Ling Xu1Lian Liu2Danlin Yao3Xiangbo Zeng4Yikai Zhang5Yikai Zhang6Jing Lai7Jun Zhong8Xianfeng Zha9Runhui Zheng10Yuhong Lu11Minming Li12Zhenyi Jin13Sudheendra Hebbar Subramanyam14Shaohua Chen15Xin Huang16Yangqiu Li17Yangqiu Li18The Clinical Medicine Postdoctoral Research Station, Department of Hematology, First Affiliated Hospital; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaLaboratory Center, Tianhe Nuoya Bio-Engineering Co. Ltd, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaDepartment of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, China Guangzhou, ChinaDepartment of Hematology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaDepartment of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaDepartment of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Clinical Medicine Postdoctoral Research Station, Department of Hematology, First Affiliated Hospital; Jinan University, Guangzhou, ChinaKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine; Jinan University, Guangzhou, ChinaDespite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site, and peripheral blood (PB) and understanding how T cells are affected by AML induction chemotherapy or the influence of age may help to select patients who may benefit from ICI treatment. In this study, we comprehensively compared the distribution of PD-1 and TIGIT, two of the most well-studied IC proteins, in PB and BM T cells from AML patients at the stages of initial diagnosis, complete remission (CR), and relapse-refractory (R/R) disease after chemotherapy. Our results show that PD-1 was generally expressed higher in PB and BM T cells from de novo (DN) and R/R patients, while it was partially recovered in CR patients. The expression of TIGIT was increased in the BM of CD8+ T cells from DN and R/R patients, but it did not recover with CR. In addition, according to age correlation analysis, we found that elderly AML patients possess an even higher percentage of PD-1 and TIGIT single-positive CD8+ T cells in PB and BM, which indicate greater impairment of T cell function in elderly patients. In addition, we found that both DN and R/R patients accumulate a higher frequency of PD-1+ and TIGIT+ CD8+ T cells in BM than in corresponding PB, indicating that a more immunosuppressive microenvironment in leukemia BM may promote disease progression. Collectively, our study may help guide the combined use of anti-PD-1 and anti-TIGIT antibodies for treating elderly AML patients and pave the way for the exploration of strategies for reviving the immunosuppressive BM microenvironment to improve the survival of AML patients.https://www.frontiersin.org/articles/10.3389/fonc.2021.686156/fullPD-1TIGITacute myeloid leukemiaimmune-checkpointsT cellbone marrow |
| spellingShingle | Ling Xu Ling Xu Lian Liu Danlin Yao Xiangbo Zeng Yikai Zhang Yikai Zhang Jing Lai Jun Zhong Xianfeng Zha Runhui Zheng Yuhong Lu Minming Li Zhenyi Jin Sudheendra Hebbar Subramanyam Shaohua Chen Xin Huang Yangqiu Li Yangqiu Li PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow Frontiers in Oncology PD-1 TIGIT acute myeloid leukemia immune-checkpoints T cell bone marrow |
| title | PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow |
| title_full | PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow |
| title_fullStr | PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow |
| title_full_unstemmed | PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow |
| title_short | PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow |
| title_sort | pd 1 and tigit are highly co expressed on cd8 t cells in aml patient bone marrow |
| topic | PD-1 TIGIT acute myeloid leukemia immune-checkpoints T cell bone marrow |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.686156/full |
| work_keys_str_mv | AT lingxu pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT lingxu pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT lianliu pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT danlinyao pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT xiangbozeng pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT yikaizhang pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT yikaizhang pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT jinglai pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT junzhong pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT xianfengzha pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT runhuizheng pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT yuhonglu pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT minmingli pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT zhenyijin pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT sudheendrahebbarsubramanyam pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT shaohuachen pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT xinhuang pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT yangqiuli pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow AT yangqiuli pd1andtigitarehighlycoexpressedoncd8tcellsinamlpatientbonemarrow |