Natural killer cell homing and trafficking in tissues and tumors: from biology to application

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 29, 2022

Abstract Natural killer (NK) cells, a subgroup of innate lymphoid act as the first line defense against cancer. Although some evidence shows that NK cells can develop in secondary tissues, mainly bone marrow (BM) and egress into blood circulation when they mature. They then migrate to settle down peripheral though special subsets home back BM or organs. Owing its success allogeneic adoptive transfer for cancer treatment “off-the-shelf” potential, cell-based immunotherapy is attracting increasing attention various cancers. However, insufficient infiltration adoptively transferred limits clinical utility, especially solid tumors. Expansion engineered chimeric antigen receptor (CAR) ex vivo prior by using cytokines alters profiles chemokine receptors, which affects tumor tissue. Several factors control cell trafficking homing, including cell-intrinsic (e.g., transcriptional factors), cell-extrinsic integrins, selectins, chemokines their corresponding signals induced cytokines, sphingosine-1-phosphate (S1P), etc.), cellular microenvironment. Here, we summarize mechanisms homing at steady state during development, aiming improve immunotherapy.

Language: Английский

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Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(1), P. e003497 - e003497

Published: Jan. 1, 2022

Background Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous carcinoma (ESCC); however, little is known about the efficacy of PD-1 as neoadjuvant therapy resectable ESCC. We aim to assess safety and feasibility using combination chemotherapy Methods Patients previously untreated, (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles treatment camrelizumab, nab-paclitaxel, carboplatin before undergoing surgical resection approximately 6–9 weeks after first cycle. Results Between January 2020 September 2020, 37 screened, whom 23 The therapeutic regimen had an acceptable side effect profile, no delays surgery observed. Severe (grade 3–4) treatment-related adverse events included neutropenia (9 23, 39.1%) leukopenia (2 8.7%). objective response disease control rates 90.5% 100%, respectively. Twenty surgery, R0 was achieved all cases. Five (25%) a pathological complete (PCR) 10 (50%) major response. proportion high mutation burden expression programmed death-ligand (PD-L1) primary significantly higher PCR group than non-PCR (p=0.044). number infiltrating PD-L1 + CD163 cells lower (p=0.017). Conclusions Neoadjuvant camrelizumab plus nab-paclitaxel manageable effects induced patients, demonstrating its antitumor Trial registration ChiCTR2000028900.

Language: Английский

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Targeting the RNA m6A modification for cancer immunotherapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: March 16, 2022

Abstract N 6 -methyladenosine (m A) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription translation programs that promote cancer occurrence progression. Although defective gene regulation resulting from m A often affects oncogenic tumor-suppressing networks, can also modulate tumor immunogenicity immune cells involved in anti-tumor responses. Understanding this counterintuitive concept aid design new drugs target to potentially improve outcomes immunotherapies. Here, we provide an up-to-date comprehensive overview how modifications intrinsically affect alterations cell extrinsically responses microenvironment (TME). We review strategies for modulating endogenous immunity discuss challenge reshaping TME. Strategies include: combining specific efficient inhibitors against regulators with checkpoint blockers; generating effective programmable gene-editing system enables manipulation individual sites; establishing enhance T or natural killer cells; using nanoparticles specifically tumor-associated macrophages (TAMs) deliver messenger RNA small interfering A-related molecules repolarize TAMs, enabling them remodel The goal help field understand shape TME so better immunotherapy be designed developed.

Language: Английский

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Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Dec. 1, 2020

Natural killer (NK) cells are a critical component of the innate immune system. Chimeric antigen receptors (CARs) re-direct NK toward tumor carrying corresponding antigens, creating major opportunities in fight against cancer. CAR have potential for use as universal without need human leukocyte matching or prior exposure to tumor-associated antigens. Exciting data from recent clinical trials renewed interest field cancer immunotherapy due production "off-the-shelf" anti-cancer immunotherapeutic products. Here, we provide an up-to-date comprehensive overview advancements key areas cell research and identify under-investigated areas. We summarize improvements design structure, advantages disadvantages using alternative T therapy, list sources obtain cells. In addition, antigens targeted by detail challenges expanding transducing production. additionally discuss barriers effective treatment suggest solutions improve function, proliferation, persistence, therapeutic effectiveness, safety solid liquid tumors.

Language: Английский

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Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: Feb. 11, 2019

Despite advances in the diagnostic and therapeutic modalities, prognosis of several solid tumor malignancies remains poor. Different factors associated with tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between cells immune cells, hypoxic immunosuppressive effects microenvironment result treatment resistant metastatic phenotype. Over past years, immunotherapy has emerged as an attractive option against multiple malignancies. The unique ability natural killer (NK) to target cancer without antigen specificity makes them ideal candidate for use tumors. However, outcomes adoptive NK cell infusions into patients have been disappointing. Extensive studies done investigate different strategies improve function, trafficking targeting. Use cytokines cytokine analogues well described utilized enhance proliferation, stimulation persistence cells. Other techniques like blocking human leukocyte antigen-killer receptors (KIR) interactions anti-KIR monoclonal antibodies, preventing CD16 receptor shedding, increasing expression activating NKG2D, immunocytokines checkpoint inhibitors can mediated cytotoxicity. Using genetically modified chimeric bispecific trispecific engagers, be effectively redirected improving their cytotoxic potential. In this review, we these highlighted need further optimize clinical outcome based

Language: Английский

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