• Title/Summary/Keyword: Checkpoint inhibitors

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Pembrolizumab-related autoimmune hemolytic anemia in a patient with metastatic lung adenocarcinoma: a case report

  • Baek, Dong Won;Chae, Yee Soo
    • Journal of Yeungnam Medical Science
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    • v.38 no.4
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    • pp.366-370
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    • 2021
  • Immune checkpoint inhibitors (ICIs) have become the main drugs for programmed cell death receptor-1 or ligand-1 expressing non-small cell lung cancer (NSCLC) combined with conventional chemotherapy. ICIs are generally more tolerable than cytotoxic chemotherapies in terms of toxicity, and ICI-related adverse events are mild and manageable. However, these drugs may lead to unexpected severe adverse events such as immune-related hematologic toxicities, which could be life-threatening. Here, a rare case of a pembrolizumab-related adverse event in a patient with NSCLC who showed early-onset hemolytic anemia and recovered by high-dose steroid and a series of plasma exchanges is reported.

The Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy

  • Kim, Jaeho;Lee, Heung Kyu
    • Molecules and Cells
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    • v.44 no.5
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    • pp.356-362
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    • 2021
  • An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.

TcellInflamedDetector: an R package to distinguish T cell inflamed tumor types from non-T cell inflamed tumor types

  • Yang, San-Duk;Park, Hyun-Seok
    • Genomics & Informatics
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    • v.20 no.1
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    • pp.13.1-13.4
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    • 2022
  • A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non-T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non-T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non-T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

Lumbosacral polyradiculoneuropathy associated with combination therapy of nivolumab and ipilimumab

  • Cho, Eun Bin;Kim, Seung Joo;Yang, Tae-Won;Jung, Seunguk;Jeong, Heejeong;Park, Ki-Jong
    • Annals of Clinical Neurophysiology
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    • v.24 no.1
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    • pp.26-29
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    • 2022
  • Immune checkpoint inhibitors (ICIs) have emerged as one of the most promising therapeutic options for advanced cancers. While ICIs have improved survival in multiple cancers, their increased use is restricted by various immune-related adverse events. In this report we describe a patient with renal cell carcinoma who received a combination of ICIs, nivolumab plus ipilimumab, and who developed lumbosacral polyradiculoneuropathy. Corticosteroid use was an effective treatment for this patient.

Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer

  • Su, Min;Huang, Chun-Xia;Dai, Ai-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.905-910
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    • 2016
  • Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know

  • Luca Russo;Giacomo Avesani;Benedetta Gui;Charlotte Marguerite Lucille Trombadori;Vanda Salutari;Maria Teresa Perri;Valerio Di Paola;Elena Rodolfino;Giovanni Scambia;Riccardo Manfredi
    • Korean Journal of Radiology
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    • v.22 no.8
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    • pp.1310-1322
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    • 2021
  • Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.

Recent Progress in Immunotherapy for Advanced Gastric Cancer (진행성 위암에 대한 면역 요법의 최신 지견)

  • Byeong Seok Sohn
    • Journal of Digestive Cancer Research
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    • v.10 no.1
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    • pp.22-30
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    • 2022
  • Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

The emerging role of myeloid-derived suppressor cells in radiotherapy

  • Kang, Changhee;Jeong, Seong-Yun;Song, Si Yeol;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.38 no.1
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    • pp.1-10
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    • 2020
  • Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer

  • Lee, Yong Jun;Lee, Jii Bum;Ha, Sang-Jun;Kim, Hye Ryun
    • Molecules and Cells
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    • v.44 no.5
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    • pp.363-373
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    • 2021
  • Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.