Neoplasms in the bone marrow niches: disturbance of the microecosystem

Mu, Lili; Fang, Ke; Guo, Xingxing; Cai, Jie-Jing; Hong, Dengli

doi:10.1007/s12185-017-2193-5

Cited by 1 publication

(1 citation statement)

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“…In the BM, which is the nest of the leukemia progenitors generated and output in AML, the environment is quite complicated and resembles that of the TME in solid tumors to some degree. For example, the BM of AML patients also accumulates Treg, MDSC, and pDC cells that could inhibit the anti-leukemia immune response of T cells (24)(25)(26)(27). Increasing evidence has shown that the BM immune environment of AML patients is profoundly altered, contributing to the severity of the disease; however, there have been limited studies comparing differences in T cell dysfunction between PB and BM.…”

Section: Introductionmentioning

confidence: 99%

PD-1 and TIGIT Are Highly Co-Expressed on CD8+ T Cells in AML Patient Bone Marrow

Xu¹,

Yao²,

Zeng³

et al. 2021

Front. Oncol.

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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.

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Section: Introductionmentioning

confidence: 99%