Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients

Liu, Zhaoyun; Fu, Rong

doi:10.3389/fimmu.2021.663748

Cited by 20 publications

(13 citation statements)

References 102 publications

(148 reference statements)

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“…The immune profiling may play a crucial role in the outcome of MM [19], but probably only a complete immune evaluation will successfully predict survival in MM patients [20].…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Classical Immunoparesis in Multiple Myeloma

et al. 2022

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Multiple myeloma (MM) is a very heterogeneous hematological malignancy characterized by the proliferation of clonal plasma cells in bone marrow, leading to a decrease in normal plasma cells. The immune system plays a key role in both the pathogenesis and the prognosis of MM. A wide range of immune dysfunctions can be demonstrated in most patients at diagnosis. The presence of suppression of uninvolved immunoglobulins, also called classical immunoparesis (CIP), can be demonstrated in the majority of newly diagnosed MM (NDMM) patients, although its prognostic impact remains controversial in previous studies. Our population-based study confirms that CIP is present in most NDMM patients. It is associated with several well-known prognostic factors, including the International Staging System, being more frequent in late stages. Median overall survival in CIP+ patients was 62.4 months (CI 95%, 52.1-72.7), whereas it was not reached for those CIP-(p=0.150). Despite the absence of statistical significance, the multivariate Cox proportional hazards model endorses CIP as an independent and strong prognostic factor for overall survival in NDMM, besides age, performance status, total serum cholesterol, and the presence of 1q gain. More comprehensive studies, including complete immune profiling, are warranted to establish the role of CIP in the context of the current and emerging prognostic factors in NDMM.

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“…The immune profiling may play a crucial role in the outcome of MM [19], but probably only a complete immune evaluation will successfully predict survival in MM patients [20].…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Classical Immunoparesis in Multiple Myeloma

et al. 2022

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“…Accumulating evidences show that NK cells paly a central role in anti-tumor e cacy due to their ability to spontaneously kill tumor cells 27,28 . To date, MM has still been an enduring conundrum.Since immune dysfunction have been reported as an important part for disease progression and even in uence survival of MM patients 29,30 . Taking more study on immune cell and develop immune therapy will be a new choice for MM patients.As previous reported that the count of NK cell were increased in MM patients,but the function show exhausted 31 .Considering the advantage of NK cell count in MM patients and kill malignant cells without prior sensitization,it is easy for us to think to make a full use of NK cell to antimyeloma cell.In fact,there have been reported some way to use NK cell in MM patients investigation,like active NK cell function choice Daratumumab 32 and SLAMF7 antibody 33 , the other way is the using targeting NK cell inhibitory receptors including TIGIT, PD-1 and TIM-3 10 .However,new ways still needed since the complex regulation of NK cell function and MM immune micro-environment.…”

Section: Discussionmentioning

confidence: 99%

PIM2 kinase regulates the expression of TIGIT and energy metabolism on NK cell in multiple myeloma patients

Liu

Wang

et al. 2022

Preprint

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Background: PIM2 kinase play a vital role in the generation of plasma cell and bone loss in multiple myeloma(MM), which highly related to the tumor progression and as a potential therapy target in MM. In immune cell,PIM2 kinase involved in the regulation of lymphocyte like T cell and B cell, However, its role in NK cells remains unclear. Methods: Single-cell RNA sequencing data were analysed the expression of PIM2 kinase in NK cells from MM patients and healthy donors.Immune checkpoint expression, cell apoptosis, and NK cell function had been evaluated through flow cytometry.Then, NCBI, UCSC, JASPAR and GEPIA database were used to predict promoter of TIGIT.NK-92 cells with ETS-1 knockdown were established by using sh-RNA. Kinase functional assay (ADP-Glo) were used to confirm PIM2 inhibitor from 160 kinds of natural flavonoids compound.Samples treated with or without drugs were analyzed using mass spectrometry and RNA-seq. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR) were measured by assay kit. Result: The PIM2 kinase was highly expressed in the NK cells from MM patients based on single-cell sequencing analysis and confirmed in clinical sample by PCR and flow cytometry.Inhibition of PIM2 kinase can increase the function of NK cells and down regulation TIGIT expression. Mechanism, we confirmed that ETS-1 which was directly binding to the promoter of TIGIT was up-regulated by PIM2 kinase, which can lead the strengthened transcription of TIGIT on NK cells.Furthermore, two novel natural flavonoids compound named Kaempferol and Quercetin dihydrate as PIM2 kinase inhibitors exhibiting higher efficiency at low dose in MM cells,while influence the expression of TIGIT and energy metabolism on NK-92 cells. For in vitro experiment,PIM2 kinase inhibitors can activate NK cell killing function and decrease TIGIT expression,while promoted the apoptosis of MM cells irrespective of adding BMSCs or not in co-culture systems BMSCs. Conclusion: PIM2 kinase involved in the regulation of NK cell.Inhibiting PIM2 kinase could down-regulate the expression of TIGIT and improve energy metabolism to enhance NK cell anti myeloma cell.

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“…However, the progression of MM was not noly related to MRD,but also closely related to the exhaustion of functional immune cells, and the suppression of regulatory immune cells. [15]. Previous studies had shown that applying ow cytometry can also analyze T cells in multiple myeloma patients, and that T cell subsets such as Treg have an important role in assessing MM patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

Immune profiles in Bone marrow to predict induce therapy response for multiple myeloma patients

Liu

Shen

Han

et al. 2022

Preprint

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Purpose: To find bone marrow immune detection index which related to MM patients therapy. Method: We analyzed ninety-three newly diagnosed MM patients retrospectively and their the stage of prognosis, the clinical and induced-therapy response datasets. Result: In our study, Eight-color flow cytometry, a method commonly used to detect MM cell loads, was used to analyze seven bone marrow immune cell groups (B, NK, T, naive B, immature B, memory B, and plasmablast like cells). The percentage of B cells significantly decreased in stage III, compared with stage I patients, (P = 0.047, P = 0.038) according to the ISS and R-ISS. In the clinical characteristics, naive B cell numbers increased in the Hb(g/L)≥100 group, when compared with the Hb(g/L)< 100 group (P = 0.028). The immature B (P = 0.017), plasmablast like cell subgroups(P = 0.037) increased in MM patients, who achieved a very good partial response(VGPR), after four cycles of the new drug-based induced therapy. The ROC results indicated the combination of the seven immune subgroups had predictive values (AUC = 0.840; P < 0.0001). Conclusion: comprehensively analyze seven bone marrow immune cell subgroups can be a useful approach for predicting the induce therapy response in MM patients.

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Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients

Cited by 20 publications

References 102 publications

The Prognostic Value of Classical Immunoparesis in Multiple Myeloma

The Prognostic Value of Classical Immunoparesis in Multiple Myeloma

PIM2 kinase regulates the expression of TIGIT and energy metabolism on NK cell in multiple myeloma patients

Immune profiles in Bone marrow to predict induce therapy response for multiple myeloma patients

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