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Article: Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.

Chen, Zhangguo / John, Jessy / Wang, Jing H

2022 Volume 12, Page(s) 995434

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment including in head and neck squamous cell carcinomas (HNSCCs); however, only a fraction of HNSCC patients respond to ICI, whereas the majority fail to do so. The mechanisms ... ...

Abstract	Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment including in head and neck squamous cell carcinomas (HNSCCs); however, only a fraction of HNSCC patients respond to ICI, whereas the majority fail to do so. The mechanisms underlying such variable responses remain incompletely understood. A better understanding of such mechanisms may broaden the spectrum of responding patients and enhance the rate of ICI response. HNSCCs exhibit a high level of genetic heterogeneity, manifested as mutations or amplifications of oncogenes (e.g.,
Language	English
Publishing date	2022-10-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.995434
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: How the Signaling Crosstalk of B Cell Receptor (BCR) and Co-Receptors Regulates Antibody Class Switch Recombination: A New Perspective of Checkpoints of BCR Signaling.

Chen, Zhangguo / Wang, Jing H

Frontiers in immunology

2021 Volume 12, Page(s) 663443

Abstract: Mature B cells express B cell antigen receptor (BCR), toll-like receptors (TLR) and TNF family receptors including CD40 and B-cell activating factor receptor (BAFFR). These receptors transduce cellular signals to govern the physiological and pathological ...

Abstract	Mature B cells express B cell antigen receptor (BCR), toll-like receptors (TLR) and TNF family receptors including CD40 and B-cell activating factor receptor (BAFFR). These receptors transduce cellular signals to govern the physiological and pathological processes in B cells including B cell development and differentiation, survival, proliferation, and antibody-mediated immune responses as well as autoimmune diseases and B cell lymphomagenesis. Effective antibody-mediated immune responses require class switch recombination (CSR), a somatic DNA recombination event occurring at the immunoglobulin heavy chain (
MeSH term(s)	Animals ; B-Cell Activation Factor Receptor/metabolism ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Carrier Proteins/metabolism ; Humans ; Immunoglobulin Class Switching/genetics ; Immunoglobulin Class Switching/immunology ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, B-Cell/metabolism ; Receptors, Tumor Necrosis Factor/metabolism ; Signal Transduction ; Toll-Like Receptors/metabolism
Chemical Substances	B-Cell Activation Factor Receptor ; Carrier Proteins ; Receptors, Antigen, B-Cell ; Receptors, Tumor Necrosis Factor ; Toll-Like Receptors
Language	English
Publishing date	2021-03-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.663443
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Article ; Online: A Friction-Driven Strategy for Agile Steering Wheel Manipulation by Humanoid Robots.

Cai, Zhaoyang / Zhu, Xin / Gergondet, Pierre / Chen, Xuechao / Yu, Zhangguo

Cyborg and bionic systems (Washington, D.C.)

2023 Volume 4, Page(s) 64

Abstract: Vehicle driving can substantially enhance the maneuverability of humanoid robots. Agile steering wheel manipulation requires rapid rotation in narrow spaces such as a cab, serving as the foundation for increasing driving speed, especially in an obstacle ... ...

Abstract	Vehicle driving can substantially enhance the maneuverability of humanoid robots. Agile steering wheel manipulation requires rapid rotation in narrow spaces such as a cab, serving as the foundation for increasing driving speed, especially in an obstacle avoidance scenario. Generally, there are 3 human driving strategies, "Hand-to-Hand," "Hand-over-Hand," and "One-Hand." Based on the human driving motion data, we quantitatively analyze these strategies from 3 aspects, motion range of joint combination, motion region of the shoulder, and velocity of the manipulation. Then, a friction-driven manipulation strategy using one hand is proposed utilizing the similarity between a humanoid robot and a driver (human). It effectively addresses the requirements of both a small range of motion and rapid manipulation. To prevent the deformation of the steering wheel caused by excessive force, we construct an operating force model specifically for the steering wheel. This model accurately describes the relationship between the rotation resistance and the state of the steering wheel. In addition, we propose a quadratic programming (QP)-based control framework to servo the robot to track the end-effector position and target wrench output by this model. Finally, the effectiveness of this paper is evaluated through an obstacle avoidance scenario, achieving a maximum rotation velocity of 3.14 rad/s.
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ISSN	2692-7632
ISSN (online)	2692-7632
DOI	10.34133/cbsystems.0064
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Article ; Online: High-precision dynamic torque control of high stiffness actuator for humanoids.

Liu, Yaliang / Chen, Xuechao / Yu, Zhangguo / Yu, Han / Meng, Libo / Yokoi, Hiroshi

ISA transactions

2023 Volume 141, Page(s) 401–413

Abstract: The high stiffness actuator (HSA), applied to each joint of an electrical driven humanoid robot, can directly affect the motion performance of the torque-controlled humanoid robots. For high control performance of HSA, a high-precision dynamic torque ... ...

Abstract	The high stiffness actuator (HSA), applied to each joint of an electrical driven humanoid robot, can directly affect the motion performance of the torque-controlled humanoid robots. For high control performance of HSA, a high-precision dynamic torque control (HDTC) is proposed. The HDTC consists of two phases: (1) A novel dynamic current control is used to linearize high stiffness actuator torque control system, which can estimate and compensate the nonlinear coupling parts; (2) An enhanced internal model control is designed to ensure high tracking accuracy in the system containing noisy torque signal and even numerical differentiation signals. Benefitting from dynamic current control and the enhanced internal model control, the proposed HDTC is accurate and adaptable. Finally, the superiority of the HDTC is verified with comparative experiments.
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2012746-7
ISSN	1879-2022 ; 0019-0578
ISSN (online)	1879-2022
ISSN	0019-0578
DOI	10.1016/j.isatra.2023.06.031
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Article ; Online: Hybrid Momentum Compensation Control by Using Arms for Bipedal Dynamic Walking.

Gao, Zhifa / Chen, Xuechao / Yu, Zhangguo / Han, Lianqiang / Zhang, Jintao / Huang, Gao

Biomimetics (Basel, Switzerland)

2023 Volume 8, Issue 1

Abstract: Biped robots swing their legs alternately to achieve highly dynamic walking, which is the basic ability required for them to perform tasks. However, swinging of the swinging leg in the air will disturb the interaction between the supporting leg and the ... ...

Abstract	Biped robots swing their legs alternately to achieve highly dynamic walking, which is the basic ability required for them to perform tasks. However, swinging of the swinging leg in the air will disturb the interaction between the supporting leg and the ground and affect the upper body's balance during dynamic walking. To allow the robot to use its own intrinsic motion characteristics to maintain stable movement like a human when its lower limbs are affected by unknown disturbances during dynamic walking, the ability to use its arms to resist disturbances is essential. This article presents a hybrid momentum compensation control method for torque-controlled biped robots to adapt to unknown disturbances during dynamic walking. First, a hybrid angular momentum and linear momentum regulator is designed to compensate for the disturbance caused by the swinging leg. Second, based on real-time dynamic state changes of the legs, a mixed-momentum quadratic programming controller is designed to realize stable dynamic walking. The proposed method allows the force-controlled robot to maintain its balance while walking down an unknown platform, and it maintains good straightness in the forward direction of dynamic motion. The proposed method's effectiveness is verified experimentally on the BHR-B2 force-controlled biped robot platform.
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article
ISSN	2313-7673
ISSN (online)	2313-7673
DOI	10.3390/biomimetics8010031
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Article ; Online: Online Running-Gait Generation for Bipedal Robots with Smooth State Switching and Accurate Speed Tracking.

Meng, Xiang / Yu, Zhangguo / Chen, Xuechao / Huang, Zelin / Dong, Chencheng / Meng, Fei

Biomimetics (Basel, Switzerland)

2023 Volume 8, Issue 1

Abstract: Smooth state switching and accurate speed tracking are important for the stability and reactivity of bipedal robots when running. However, previous studies have rarely been able to synthesize these two capabilities online. In this paper, we present an ... ...

Abstract	Smooth state switching and accurate speed tracking are important for the stability and reactivity of bipedal robots when running. However, previous studies have rarely been able to synthesize these two capabilities online. In this paper, we present an online running-gait generator for bipedal robots that allows for smooth state switching and accurate speed tracking. Considering a fluctuating height nature and computational expediency, the robot is represented by a simplified variable-height inverted-pendulum (VHIP) model. In order to achieve smooth state switching at the beginning and end of running, a segmented zero moment point (ZMP) trajectory optimization is proposed to automatically provide a feasible and smooth center-of-mass (CoM) trajectory that enables the robot to stably start or stop running at the given speed. To accurately track online the desired speed during running, we propose an iterative algorithm to compute target footholds, which allows for the robot to follow the interactive desired speed after the next two steps. Lastly, a numerical experiment and the simulation of online variable speed running were performed with position-controlled bipedal robot BHR7P, and the results verified the effectiveness of the proposed methods.
Language	English
Publishing date	2023-03-10
Publishing country	Switzerland
Document type	Journal Article
ISSN	2313-7673
ISSN (online)	2313-7673
DOI	10.3390/biomimetics8010114
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Article ; Online: Signaling control of antibody isotype switching.

Chen, Zhangguo / Wang, Jing H

Advances in immunology

2019 Volume 141, Page(s) 105–164

Abstract: Class switch recombination (CSR) generates isotype-switched antibodies with distinct effector functions essential for mediating effective humoral immunity. CSR is catalyzed by activation-induced deaminase (AID) that initiates DNA lesions in the ... ...

Abstract	Class switch recombination (CSR) generates isotype-switched antibodies with distinct effector functions essential for mediating effective humoral immunity. CSR is catalyzed by activation-induced deaminase (AID) that initiates DNA lesions in the evolutionarily conserved switch (S) regions at the immunoglobulin heavy chain (Igh) locus. AID-initiated DNA lesions are subsequently converted into DNA double stranded breaks (DSBs) in the S regions of Igh locus, repaired by non-homologous end-joining to effect CSR in mammalian B lymphocytes. While molecular mechanisms of CSR are well characterized, it remains less well understood how upstream signaling pathways regulate AID expression and CSR. B lymphocytes express multiple receptors including the B cell antigen receptor (BCR) and co-receptors (e.g., CD40). These receptors may share common signaling pathways or may use distinct signaling elements to regulate CSR. Here, we discuss how signals emanating from different receptors positively or negatively regulate AID expression and CSR.
MeSH term(s)	Animals ; B-Cell Activation Factor Receptor/metabolism ; B-Lymphocytes/immunology ; Cytidine Deaminase/metabolism ; DNA Breaks, Double-Stranded ; Humans ; Immunity, Humoral/genetics ; Immunoglobulin Class Switching/genetics ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Isotypes/genetics ; Mice ; Receptors, Antigen, B-Cell/metabolism ; Recombination, Genetic ; Signal Transduction ; Toll-Like Receptors/metabolism ; Transmembrane Activator and CAML Interactor Protein/metabolism
Chemical Substances	B-Cell Activation Factor Receptor ; Immunoglobulin Heavy Chains ; Immunoglobulin Isotypes ; Receptors, Antigen, B-Cell ; TNFRSF13C protein, human ; Toll-Like Receptors ; Transmembrane Activator and CAML Interactor Protein ; AICDA (activation-induced cytidine deaminase) (EC 3.5.4.-) ; Cytidine Deaminase (EC 3.5.4.5)
Language	English
Publishing date	2019-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80226-8
ISSN	1557-8445 ; 0065-2776
ISSN (online)	1557-8445
ISSN	0065-2776
DOI	10.1016/bs.ai.2019.01.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Upright and Crawling Locomotion and Its Transition for a Wheel-Legged Robot.

Qiu, Xuejian / Yu, Zhangguo / Meng, Libo / Chen, Xuechao / Zhao, Lingxuan / Huang, Gao / Meng, Fei

Micromachines

2022 Volume 13, Issue 8

Abstract: To face the challenge of adapting to complex terrains and environments, we develop a novel wheel-legged robot that can switch motion modes to adapt to different environments. The robot can perform efficient and stable upright balanced locomotion on flat ... ...

Abstract	To face the challenge of adapting to complex terrains and environments, we develop a novel wheel-legged robot that can switch motion modes to adapt to different environments. The robot can perform efficient and stable upright balanced locomotion on flat roads and flexible crawling in low and narrow passages. For passing through low and narrow passages, we propose a crawling motion control strategy and methods for transitioning between locomotion modes of wheel-legged robots. In practical applications, the smooth transition between the two motion modes is challenging. By optimizing the gravity work of the body, the optimal trajectory of the center of mass (CoM) for the transition from standing to crawling is obtained. By constructing and solving an optimization problem regarding the posture and motion trajectories of the underactuated model, the robot achieves a smooth transition from crawling to standing. In experiments, the wheel-legged robot successfully transitioned between the crawling mode and the upright balanced moving mode and flexibly passed a low and narrow passage. Consequently, the effectiveness of the control strategies and algorithms proposed in this paper are verified by experiments.
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2620864-7
ISSN	2072-666X
ISSN	2072-666X
DOI	10.3390/mi13081252
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Article ; Online: Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders.

John, Jessy / Chen, Samantha M Y / Woolaver, Rachel A / Ge, Huaibin / Vashisht, Monika / Huang, Ziyu / Chen, Zhangguo / Wang, Jing H

Frontiers in immunology

2023 Volume 14, Page(s) 1100520

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, the responses to ICI treatment are highly variable in different individuals and the underlying mechanisms remain poorly understood. Here, we employed a mouse squamous cell ...

Abstract	Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, the responses to ICI treatment are highly variable in different individuals and the underlying mechanisms remain poorly understood. Here, we employed a mouse squamous cell carcinoma (SCC) model where tumor-bearing recipients diverged into responders (R) versus non-responders (NR) upon anti-PD-L1 treatment. We performed in-depth TCRβ sequencing with immunoSEQ platform to delineate the differences in CD8 tumor-infiltrating lymphocytes (TILs). We found that R and NR CD8 TILs both exhibited evidence of clonal expansion, suggesting activation regardless of response status. We detected no differences in clonal expansion or clonal diversity indexes between R vs. NR. However, the top expanded (>1%) TCRβ clonotypes appeared to be mutually exclusive between R and NR CD8 TILs, showing a preferential expansion of distinct TCRβ clonotypes in response to the same SCC tumor in R vs. NR. Notably, the mutual exclusivity of TCR clonotypes in R vs. NR was only observed when top TCRβ clonotypes were counted, because such top-expanded clonotypes are present in the opposite outcome group at a much lower frequency. Many TCRβ sequences were detected in only one recipient at a high frequency, implicating highly individualized anti-tumor immune responses. We conclude that differences in the clonal frequency of top TCR clonotypes between R and NR CD8 TILs may be one of the factors underlying differential anti-PD-L1 responses. This notion may offer a novel explanation for variable ICI responses in different individuals, which may substantially impact the development of new strategies for personalized cancer immunotherapy.
MeSH term(s)	Animals ; Mice ; CD8-Positive T-Lymphocytes ; Immunotherapy ; Receptors, Antigen, T-Cell
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1100520
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Article ; Online: TRAF2/3 deficient B cells resist DNA damage-induced apoptosis via NF-κB2/XIAP/cIAP2 axis and IAP antagonist sensitizes mutant lymphomas to chemotherapeutic drugs.

Vashisht, Monika / Ge, Huaibin / John, Jessy / McKelvey, Harlie A / Chen, Jingxin / Chen, Zhangguo / Wang, Jing H

Cell death & disease

2023 Volume 14, Issue 9, Page(s) 599

Abstract: Deletion of TRAF2 or TRAF3 in B cells prolongs their survival. However, it remains unknown whether deletion of such factors affects B cells' ability to tolerate DNA damage, which can be induced by chemotherapeutics and cause apoptosis. Genetic ... ...

Abstract	Deletion of TRAF2 or TRAF3 in B cells prolongs their survival. However, it remains unknown whether deletion of such factors affects B cells' ability to tolerate DNA damage, which can be induced by chemotherapeutics and cause apoptosis. Genetic alterations of TRAF2 or TRAF3 are observed in subsets of human B-cell lymphomas and B cell-specific deletion of TRAF3 led to lymphoma development in aged mice. However, it remains unknown whether double deficiency of TRAF2 and TRAF3 accelerates B-cell lymphomagenesis. Here, we showed that B cell-specific TRAF2/3 double deficient (B-TRAF2/3-DKO) B cells were remarkably more resistant to DNA damage-induced apoptosis via upregulating cIAP2 and XIAP, which in turn attenuates caspase-3 activation. Mechanistically, resistance to DNA damage-induced apoptosis required NF-κB2, which effects by upregulating XIAP and cIAP2 transcription. B-TRAF2/3-DKO mice exhibited a shorter lifespan and succumbed to splenomegaly and lymphadenopathy. Unexpectedly, the incidence of B-cell lymphoma development in B-TRAF2/3-DKO mice was relatively rare (∼10%). Sequencing B cell receptor repertoire of diseased B cells revealed that TRAF2/3 deficiency caused abnormal oligoclonal or clonal expansion of B cells. While a fraction of mutant B cells (25-43%) from aged diseased mice harbored recurrent chromosomal translocations, primary B cells isolated from young B-TRAF2/3-DKO mice had no detectable chromosomal alterations, suggesting that TRAF2/3 deficiency per se does not cause evident genomic instability in B cells. Chemo-resistant TRAF3-deficient B-cell lymphomas were sensitized to chemotherapeutic drugs by blocking IAP activity using IAP antagonist. We conclude that double deficiency of TRAF2 and TRAF3 does not accelerate B-cell lymphomagenesis. Our studies provide insight into mechanisms regulating DNA damage-induced apoptosis and may help develop effective therapies targeting mutant B-cell lymphomas using IAP antagonist.
MeSH term(s)	Humans ; Animals ; Mice ; Aged ; TNF Receptor-Associated Factor 2/genetics ; TNF Receptor-Associated Factor 3/genetics ; NF-kappa B p52 Subunit ; Lymphoma ; Apoptosis/genetics ; DNA Damage ; Lymphoma, B-Cell/drug therapy ; Lymphoma, B-Cell/genetics ; X-Linked Inhibitor of Apoptosis Protein
Chemical Substances	TNF Receptor-Associated Factor 2 ; TNF Receptor-Associated Factor 3 ; NF-kappa B p52 Subunit ; XIAP protein, human ; X-Linked Inhibitor of Apoptosis Protein
Language	English
Publishing date	2023-09-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06122-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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