scholarly journals Antitumor effect on immune control points (PD-1/PD-L1) in malignant neoplasms

2021 ◽  
Vol 20 (4) ◽  
pp. 78-84
Author(s):  
V. V. Saevets ◽  
A. Y. Shamanova ◽  
D. M. Rostovcev
Keyword(s):  
Signaling Pathway ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Response ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Immunohistochemical Method ◽  
Malignant Neoplasms ◽  
Control Points ◽  
Immune Control

Introduction. Immunotherapy of malignant neoplasms is a dynamically developing field. Diagnostic possibilities in determining the biomarkers of the tumor response to immunotherapy are discussed. The search for new diagnostic «points» of response is being conducted on the basis of detailed studies of carcinogenesis and cellular biological processes in tumor and unchanged tissues. The aim of this work is to highlight one of the promising points of influence of immunotherapy of malignant tumors of various localizations at the present stage (the PD1/PD-L1 signaling pathway), taking into account the available possibilities of application in practice in the Russian Federation. The analysis of the published activity on immunotherapy with immune checkpoint inhibitors in various malignant tumors was carried out. The search for information research sources was conducted in the open systems E-Library, National Library of Medicine (Pubmed), Cochrane Library for the last 10 years. The article analyzes the progress and prospects in the immunotherapy of malignant tumors of various localizations, including the experience of using the PD-1 inhibitor pembrolizumab in the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine. Information on the use of key diagnostic biomarkers for the prognosis and evaluation of the tumor response to this therapy option is highlighted. The prognostic and diagnostic significance of biomarkers already implemented in practice (PD-L1, MSI) is discussed in the scientific press. Successful immunotherapy has been described in the treatment of uterine body cancer, colon cancer, and colorectal cancer. At the same time, the results of the study of the effectiveness of immunotherapy in uveal melanoma are debatable. Conclusion. The effect on the PD1/PD-L1 signaling pathway with the use of immune checkpoint inhibitors (pembrolizumab, atezolizumab, etc.) is one of the promising directions in the treatment of ZNO of various localizations. The determination of a number of biomarkers by immunohistochemical method, by PCR (PD-L1 receptor, MSI) allows us to identify those cases of ZNO, immunotherapy of which can give a positive effect. New approaches are being sought to influence the signaling pathways of immune control points through the development of new combined drugs. And research is also continuing to determine the predictivity of already used biomarkers of the response to immunotherapy.

Atezolizumab-induced myositis and myocarditis in a patient with metastatic urothelial carcinoma

2020 ◽  
Vol 13 (12) ◽  
pp. e236357
Author(s):  
Mary Sessums ◽  
Siva Yarrarapu ◽  
Pramod K Guru ◽  
Devang K Sanghavi
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Basic Knowledge ◽  
Malignant Neoplasms ◽  
Diverse Range ◽  
History Of ◽  
Metastatic Urothelial Carcinoma ◽  
Acute Hypercapnic Respiratory Failure

Immune checkpoint inhibitors have revolutionised cancer therapy in the past decade. Although they have been indicated to treat a diverse range of malignant neoplasms, they are also associated with various immune-related adverse effects. We report the case of a 74-year-old man with a history of urothelial carcinoma who had atezolizumab-induced myocarditis and myositis resulting in acute hypercapnic respiratory failure, despite the discontinuation of atezolizumab and aggressive treatment with corticosteroids. This case highlights the importance of a multidisciplinary approach for early diagnosis and treatment of immune-related adverse events. Physicians must be aware of the risks associated with immune checkpoint inhibitors and have a basic knowledge regarding their management.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shunichi Yanai ◽  
Yosuke Toya ◽  
Tamotsu Sugai ◽  
Takayuki Matsumoto
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Architectural Distortion ◽  
Management Guidelines ◽  
Crypt Abscess ◽  
Gastrointestinal Adverse Events ◽  
Histopathologic Findings

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

scholarly journals 299 Cancer immune control by immune checkpoint inhibitors requires senescence

2019 ◽  
Vol 139 (9) ◽  
pp. S266
Author(s):  
E. Brenner ◽  
B.F. Schörg ◽  
T. Wieder ◽  
F. Hilke ◽  
C. Schroeder ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Control

scholarly journals Mutations Status of Chemokine Signaling Pathway Predict Prognosis of Immune Checkpoint Inhibitors in Colon Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Anqi Lin ◽  
Wentao Xu ◽  
Peng Luo ◽  
Jian Zhang
Keyword(s):  
Signaling Pathway ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Colon Adenocarcinoma ◽  
Cox Regression Analysis ◽  
Chemokine Signaling ◽  
Number Of Patients ◽  
Chemokine Signaling Pathway ◽  
The Relationship

In recent years, tumor immunotherapy has become an important treatment program and popular research focus. However, the use of immune checkpoint inhibitors (ICI) in the treatment of colorectal cancer still has limitations due to the current markers only being able to predict the prognosis of a small number of patients. As the chemokine signaling pathway can promote the anti-tumor response of the immune system by recruiting immune cells, we explored the relationship between mutations in the chemokine signaling pathway and the prognosis of colon adenocarcinoma (COAD) patients receiving ICI treatment. To analyze the relationship between chemokine mutation status and the prognosis of patients receiving ICI treatment, clinical and mutation data, with immunotherapy, for a COAD cohort was obtained from “cbioportal.” Then, combining this with COAD cohort data from The Cancer Genome Atlas (TCGA) database, the panorama of gene mutation, immunogenicity, and difference in tumor microenvironment (TME) of chemokine pathways with different mutation statuses were analyzed. High-mut status has been proved to be a prognostic indicator of COAD patients receiving ICI treatment by Univariate and Multivariate Cox regression analysis. CIBERSORT analysis showed that the infiltration degree of M1 macrophages, neutrophils, and activated natural killer (NK) cells was higher in those with high-mut status. Immunogenicity of the high-mut group was also significantly increased, with the mutation number of tumor mutation burden (TMB), neoantigen load (NAL), DNA damage repair (DDR) pathway and microsatellite instability biomarker (MSI-H) being significantly higher. In this study, we found that the mutation state of chemokine pathways is closely associated with the prognosis of COAD patients undergoing ICI treatment. The higher number of TMB, NAL, and DDR mutations and inflammatory TME, may be the mechanism of behind a better prognosis. This discovery provides a possible idea for ICI therapy of COAD.

scholarly journals Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Zhan ◽  
Hong-fang Feng ◽  
Han-qing Liu ◽  
Lian-tao Guo ◽  
Chuang Chen ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Cytotoxic T Lymphocyte ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Killing Effect ◽  
Cell Death Gene

Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.

Immune-related adverse events associated with immune-checkpoint inhibitors therapy in Mexican patients: Experience at a single center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14580-e14580
Author(s):  
Iván Romarico Romarico Gonzalez Espinoza ◽  
Neil Cortés Escobar ◽  
Mariana Chiquillo-Domínguez ◽  
Gabriela Juárez Salazar ◽  
Julio Cesar Garibay Diaz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Chemotherapeutic Agents ◽  
Real World Data ◽  
Non Melanoma Skin Cancer ◽  
Grade 3 ◽  
Patients Experience

e14580 Background: The use of immune-checkpoint inhibitors (ICIs) for solid malignancies is rapidly rising, and many new agents and treatment combinations are in development. However, ICIs have a unique side-effect profile of immune-related adverse events (irAEs) compared with chemotherapeutic agents or targeted therapies. The aim of this work was to describe the irAEs in diverse types of malignant tumors using real-world data. Methods: This is a retrospective and descriptive study of patients with diverse types of advanced malignancies treated with immunotherapy at Centro Oncológico Integral of the Hospital Ángeles in Puebla, México; during the period 2016-2020. Data about the primary neoplasm, ICIs, irAEs, organ system affected, grade and treatment was collected. Clinical and laboratory parameters were obtained by reviewing medical records. Results: A total of 117 patients were included, median age of 65 years, of which 63.2% were male and 36.8% were female. The most frequent neoplasms treated with ICIs were: lung (27.4%), kidney (16.2%), melanoma (12.8%), hepatocellular (9.4%), breast (8.5%), non-melanoma skin cancer (6.0%), mesothelioma (4.3%) and other tumors (15.3%). 39.3% of the patients had no metastases, 41.9% had metastases to at least 1 or 2 sites, and 18.8% to 3 or more sites. The types of ICIs were: nivolumab (35.0%), pembrolizumab (28.2%), atezolizumab (23.9%), ipilimumab + nivolumab (12.0%) and durvalumab (0.9%). The most frequent irAEs were: gastrointestinal (61.5%), neurologic (46.2%), pulmonary (38.5%), metabolic (32.5%) and hematologic (29.1%). 39.3% of the irAEs were reported as grade 1, 31.6% as grade 2, 14.5% as grade 3 and 2.6% as grade 4. Conclusions: Our work shows the incidence of irAEs in a poorly studied population and provides new data that complement that reported by other works, however, further prospective studies are necessary.[Table: see text]

scholarly journals Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Koji Imoto ◽  
Motoyuki Kohjima ◽  
Tomonobu Hioki ◽  
Tomoyuki Kurashige ◽  
Miho Kurokawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Biopsy ◽  
Clinical Features ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Japanese Patients ◽  
Malignant Neoplasms ◽  
Drug Induced

Aim. Immune checkpoint inhibitors (ICIs) have improved the survival rate of patients carrying various malignant neoplasms. Despite their efficacy, ICIs occasionally induce liver injury as an immune-related adverse event (irAE). This study aimed to reveal the clinical features of the hepatic irAE in Japanese patients. Methods. Among 387 patients treated with ICIs, those who developed drug-induced liver injury were investigated. We also describe the histological findings and clinical courses of four patients with hepatic irAE who underwent liver biopsy. Results. Among the 56 patients with all-grade liver injury, only 11 (19.6%) showed hepatocellular-type liver injury, which resembled autoimmune hepatitis. Thirty-four patients (60.7%) developed cholestatic or mixed-type liver injury, although only one patient showed abnormal image findings in the bile duct. Most patients with grade ≤2 liver injury improved spontaneously, while two patients with biliary dysfunction required ursodeoxycholic acid or prednisolone. Among eight patients with grade ≥3 liver injury, three required no immunosuppressants and five were treated with prednisolone (three of five patients required other types of immunosuppressants). Four patients in the case series showed diverse clinical features in terms of hepatotoxic pattern, symptoms, and the interval time between the initiation of immunotherapy and the onset of the hepatic irAE. Conclusions. Our findings suggest that ICIs could cause microscopic biliary disorder without any abnormal image finding. Because the hepatic irAE presents diverse clinical features, liver biopsy is recommended to provide appropriate treatments.

DC-HIL/Gpnmb Is a Negative Regulator of Tumor Response to Immune Checkpoint Inhibitors

2019 ◽  
Vol 26 (6) ◽  
pp. 1449-1459 ◽  
Author(s):  
Jin-Sung Chung ◽  
Vijay Ramani ◽  
Masato Kobayashi ◽  
Farjana Fattah ◽  
Vinita Popat ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Negative Regulator

scholarly journals Immunotherapy in head and neck cancer

2019 ◽  
Vol 65 (2) ◽  
Author(s):  
Mateusz Sikora ◽  
Rafał Becht
Keyword(s):  
Immune System ◽  
Head And Neck ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Malignant Neoplasms ◽  
Cell Lung Carcinoma ◽  
Positive Effects

Immunotherapy is a method for the systemic treatment of malignant neoplasms. It is based on the abolition of the immunosuppressive effect of cancer cells and is meant to mobilize the host’s immune system to actively combat with the disease. The group of cancers which are closely connected with the immune system includes: melanoma, non-small cell lung carcinoma (NSCLC), renal cancer, colon cancer, Hodgkin’s lymphoma, and head and neck squamous cell carcinoma (HNSCC). Currently, cancer immunotherapy involves treatment with immune checkpoint inhibitors, therapeutic cancer vaccines, oncolytic virotherapy, and monoclonal antibodies. In the case of HNSCC, the most frequently used method is treatment with immune checkpoint inhibitors. An example of an immunological checkpoint is programmed cell death protein-1 (PD-1), which may be activated in the process of carcinogenesis to repeal immune surveillance, favouring the development of neoplasm. The function of immune checkpoint inhibitors is based on abolition of the immunosuppressive influence of cancerous cells. Clinical trials show the positive effects of treating HNSCC with immunotherapy in certain patients. In comparison to standard systemic treatment with chemotherapy, immunotherapy rarely causes treatment-related adverse events (TRAEs). Greater survival and treatment response are factors which encourage the further development of immuno-oncology. In this article, we present a review of literature concerning the use of immunotherapy in the treatment of HNSCC.

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