Molecular Perspectives of SARS-CoV-2: Pathology, Immune Evasion, and Therapeutic Interventions

Shah, Masaud,Woo, Hyun Goo Korean Society for Molecular and Cellular Biology 2021 Molecules and cells Vol.44 No.6

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.

Effect of TLR4 and B7-H1 on Immune Escape of Urothelial Bladder Cancer and its Clinical Significance

Wang, Yong-Hua,Cao, Yan-Wei,Yang, Xue-Cheng,Niu, Hai-Tao,Sun, Li-Jiang,Wang, Xin-Sheng,Liu, Jing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background/Aim: Toll-like receptor 4 (TLR4) and B7-H1, both normally expressed restricted to immune cells, are found to be aberrantly expressed in a majority of human tumors and may play important roles in regulation of tumor immunity. It has been shown that urothelial bladder cancer (UBC) patients can manifest tumoral immune escape which may be a potential critical factor in tumor pathogenesis and progression. However, so far, the mechanisms of UBC-related immune escape have not been clarified. The aim of this study was to investigate the effect of TLR4 and B7-H1 on immune escape of UBC. Methods: Bladder cancer T24 cells were pre-incubated with LPS and co-cultured with tumor specific CTLs. CTL cytotoxicity and apoptosis rates were measured by MTT assay and flow cytometry, respectively. The effects of an ERK inhibitor on B7-H1 expression and CTL cytotoxicity against T24 cells were also evaluated. In addition, TLR4, B7-H1 and PD-1 protein expression was analyzed by immunohistochemistry in 60 UBC specimens and 10 normal urothelia. Results: TLR4 activation protected T24 cells from CTL killing via B7-H1 overexpression. However PD98059, an inhibitor of ERK, enhanced CTL killing of T24 cells by reducing B7-H1 expression. TLR4 expression was generally decreased in UBC specimens, while B7-H1 and PD-1 were greatly overexpressed. Moreover, expression of both B7-H1 and PD-1 was significantly associated with UICC stage and WHO grade classification. Conclusions: TLR4 and B7-H1 may contribute to immune escape of UBC. Targeting B7-H1 or the ERK pathway may offer new immunotherapy strategies for bladder cancer.

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

( Nayoung Kim ),( Dong-hee Lee ),( Woo Seon Choi ),( Eunbi Yi ),( Hyojeong Kim ),( Jung Min Kim ),( Hyung-seung Jin ),( Hun Sik Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.1

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers. [BMB Reports 2021; 54(1): 44-58]

두경부암에서 면역회피 기전과 면역항암제 치료

장현(Hyun Chang) 대한두경부종양학회 2017 대한두경부 종양학회지 Vol.33 No.1

두경부 편평상피세포암은 전세계적으로 6번째로 흔하며 예후가 불량한 암종이다. 면역 감시는 두경부암의 발생과 진행을 억제하는 중요한 기전으로 알려져 있다. 두경부암세포는 면역 감시를 T세포의 관용을 유도하거나 체크포인트를 통한 T세포 기능을 억제하는 등의 방법으로 회피할 수 있다. 한편 진행성 두경부암 임상연구에서 체크포인트 억제제는 명확한 항종양효과를 입증하였다. 이처럼 면역항암제가 중요한 암치료 방법으로 떠오르는 이때에 본 종설은 두경부암의 면회회피 기전 및 임상적용근거에 대한 최근 지식을 정리하였다. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high morbidity and mortality. Immune surveillance is well recognized as an important mechanism to prevent development or progression of HNSCC. HNSCC can escape the immune system through multiple mechanisms including development of tolerance in T cells and inhibition of T-cell-related pathways, generally referred to as checkpoint inhibitors. Recent clinical trials have demonstrated a clear advantage in advanced HNSCC patients treated with immune checkpoint blockade. Right at the front of the new era of immunotherapy, we will review current knowledge of immune escape mechanisms and clinical implication for HNSCC.

Roles of Matrix Metalloproteinases in Tumor Metastasis and Angiogenesis

Yoon, Sang-Oh,Park, Soo-Jin,Yun, Chang-Hyun,Chung, An-Sik Korean Society for Biochemistry and Molecular Biol 2003 Journal of biochemistry and molecular biology Vol.36 No.1

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

Roles of Matrix Metalloproteinases in Tumor Metastasis and Angiogenesis

Yoon, Sang-Oh,Park, Soo-Jin,Yun, Chang-Hyun,Chung An-sik 한국생화학분자생물학회 2003 BMB Reports Vol.36 No.1

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, reheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot preform successful metastasis. The activities of MMPs are hightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

Recent Advances in the Development of TGF-β Signaling Inhibitors for Anticancer Therapy

이호재 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.4

TGF-β is a multifunctional cytokine that plays an important role in both physiologic and pathologic processes, including cancer. Importantly, TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor or a tumor promoter, depending on the stage of tumor development. The aberrantly upregulated production of TGF-β has been strongly implicated in tumor progression, angiogenesis, and metastasis, as well as immune evasion. Therefore, hyperactivated TGF-β signaling is considered a potential therapeutic target for cancer therapy. Numerous inhibitors of overactivated TGF-β signaling have been developed, and some of them are currently in clinical trials. This review focuses on the TGF-β signaling that contributes to tumor progression and immune evasion in the tumor microenvironment and presents recent achievements on TGF-β signaling inhibition as a single or combined therapeutic approach in cancer therapy. Key Words TGF-b, Tumor microenvironment, Tumor escape, Antineoplastic agents, Immune checkpoint inhibitors

Immunotherapy in Head and Neck Squamous Cell Cancer

Nerina Denaro,Marco Carlo Merlano 대한이비인후과학회 2018 Clinical and Experimental Otorhinolaryngology Vol.11 No.4

Prognosis in relapsed metastatic head and neck squamous cell cancer (RM-HNSCC) is dismal. Platinum based chemotherapy in combination with Cetuximab is used in first-line setting, while no further validated options are available at progression. Immunotherapy has produced durable clinical benefit in some patients with RM-HNSCC although the premises are several patients are nonresponders. Studies are ongoing to determine predictive factors and the ideal setting/combination of novel immunotherapies. In this paper, we discuss the past and present of immunotherapy in head and neck cancer and provide an up-to-date information regarding the potential ways to improve immunotherapy outcomes in HNSCC.

난소암에서 인체 백혈구항원-G의 발현 분석

김현정 ( Hyun Jung Kim ),허수영 ( Soo Young Hur ),김민정 ( Min Joung Kim ),김사진 ( Sa Jin Kim ),김은중 ( Eun Jung Kim ),이원선 ( Weon Sun Lee ),박상희 ( Sang Hi Park ),이희진 ( Hee Jean Lee ),김진아 ( Jean A Kim ),박종섭 ( Jong S 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.11

Hypergravity Enhances Natural Killer Cell-mediated Cytotoxicity against Breast Cancer Cells

Minseon LEE,Dongjoo KIM,Soonjo KWON 한국생물공학회 2020 한국생물공학회 학술대회 Vol.2020 No.10