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1.
Aliment Pharmacol Ther ; 52(5): 900-901, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1388192
3.
Gynecol Endocrinol ; 37(2): 157-161, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1376255

ABSTRACT

In patients with endometriosis, ectopic endometrial tissues can escape from immune system control and survive in other tissues. The pathophysiology of endometriosis is still not fully understood. In this study, we aimed to clarify the pathophysiology of endometriosis, which is thought to be a benign but infiltrative cancer type, which has many similarities with cancer biology by determining PD-1 expression in patients with endometriosis. In this study, n = 73 cases who underwent surgery or examination at the Obstetrics and Gynecology Clinic of Sivas Cumhuriyet University Faculty of Medicine and diagnosed as endometriosis in the biopsy material taken with the pre-diagnosis of endometriosis constituted the patient group. The control group consisted of n = 64 healthy subjects without concomitant malignancy or chronic inflammatory disease. Venous whole blood samples were obtained from the study groups. PD-1 and PD-L1 levels were determined by the ELISA method from serum and plasma samples. PD-1 gene expression level was determined by RT-PCR. The PD-1 level was found to be approximately 350 ± 150 ng/L and 45 ± 17 ng/L in endometriosis and control group, respectively. While the PD-L1 level was approximately 760 ± 108 ng/L in the patients, this level was 140 ± 14 ng/L in the controls. According to the RT-PCR results, the expression of the PD-1 gene 10 times higher compared to the controls. Conclusion: The identified increase of PD-1 levels and gene expression in endometriosis groups show that immunotherapy may be used in the treatment of endometriosis.


Subject(s)
B7-H1 Antigen/blood , Endometriosis/blood , Programmed Cell Death 1 Receptor/blood , Case-Control Studies , Endometriosis/etiology , Female , Humans
6.
Med Sci Monit ; 27: e933088, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1314975

ABSTRACT

Synthetic mRNA and the expression of therapeutic proteins have accelerated vaccine development to prevent infection and heralds a new era in targeted immunotherapy in oncology. Therapeutic mRNA vaccines rely on available tumor tissue for gene sequencing analysis to compare the patient's normal cellular DNA sequences and those of the tumor. Carrier-based mRNA vaccines for cancer immunotherapy are now in development that use delivery systems based on peptides, lipids, polymers, and cationic nano-emulsions. There have also been recent developments in dendritic cell-based mRNA vaccines. For patients with available tumor tissue samples, it is possible to develop mRNA vaccines that result in the expression of tumor antigens by antigen-presenting cells (APCs), resulting in innate and adaptive immune responses. Ongoing developments in mRNA immunotherapy include modifications in the route of administration and combined delivery of multiple mRNA vaccines with checkpoint inhibitors. This Editorial aims to present a brief overview of how mRNA immunotherapy may change the therapeutic landscape of personalized medicine for patients with solid malignant tumors.


Subject(s)
Cancer Vaccines/immunology , Neoplasms/immunology , Neoplasms/therapy , RNA, Messenger/immunology , Vaccines, Synthetic/immunology , Humans , Immunotherapy/methods , Medical Oncology/methods , Precision Medicine/methods
7.
Lancet Rheumatol ; 3(6): e447-e459, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1307285

ABSTRACT

The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

8.
Can J Kidney Health Dis ; 8: 20543581211014745, 2021.
Article in English | MEDLINE | ID: covidwho-1247564

ABSTRACT

RATIONALE: Immune checkpoint inhibitors are monoclonal antibodies used in the treatment of various types of cancers. The downside of using such molecules is the potential risk of developing immune-related adverse events. Factors that trigger these autoimmune side effects are yet to be elucidated. Although any organ can potentially be affected, kidney involvement is usually rare. In this case report, we describe the first known instance of a patient being treated with an inhibitor of programmed death-ligand 1 (anti-PD-L1, a checkpoint inhibitor) who develops acute tubulointerstitial nephritis after contracting the severe acute respiratory syndrome coronavirus 2. PRESENTING CONCERNS OF THE PATIENT: A 62-year-old patient, on immunotherapy treatment for stage 4 squamous cell carcinoma, presents to the emergency department with symptoms of lower respiratory tract infection. Severe acute kidney injury is discovered with electrolyte imbalances requiring urgent dialysis initiation. Further testing reveals that the patient has contracted the severe acute respiratory syndrome coronavirus 2. DIAGNOSIS: A kidney biopsy was performed and was compatible with acute tubulointerstitial nephritis. INTERVENTIONS: The patient was treated with high dose corticosteroid therapy followed by progressive tapering. OUTCOMES: Rapid and sustained normalization of kidney function was achieved after completion of the steroid course. NOVEL FINDINGS: We hypothesize that the viral infection along with checkpoint inhibitor use has created a proinflammatory environment which led to a loss of self-tolerance to renal parenchyma. Viruses may play a more important role in the pathogenesis of autoimmunity in this patient population than was previously thought.

9.
Immunopharmacol Immunotoxicol ; 43(3): 259-264, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1238100

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Omalizumab/therapeutic use , Signal Transduction/drug effects , Humans , Immunoglobulin E/immunology , Interferon-alpha/immunology , Omalizumab/immunology , Signal Transduction/immunology , Toll-Like Receptor 7/immunology
10.
Cancer Metab ; 9(1): 24, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1236573

ABSTRACT

BACKGROUND: Neuroblastoma accounts for 7% of paediatric malignancies but is responsible for 15% of all childhood cancer deaths. Despite rigorous treatment involving chemotherapy, surgery, radiotherapy and immunotherapy, the 5-year overall survival rate of high-risk disease remains < 40%, highlighting the need for improved therapy. Since neuroblastoma cells exhibit aberrant metabolism, we determined whether their sensitivity to radiotherapy could be enhanced by drugs affecting cancer cell metabolism. METHODS: Using a panel of neuroblastoma and glioma cells, we determined the radiosensitising effects of inhibitors of glycolysis (2-DG) and mitochondrial function (metformin). Mechanisms underlying radiosensitisation were determined by metabolomic and bioenergetic profiling, flow cytometry and live cell imaging and by evaluating different treatment schedules. RESULTS: The radiosensitising effects of 2-DG were greatly enhanced by combination with the antidiabetic biguanide, metformin. Metabolomic analysis and cellular bioenergetic profiling revealed this combination to elicit severe disruption of key glycolytic and mitochondrial metabolites, causing significant reductions in ATP generation and enhancing radiosensitivity. Combination treatment induced G2/M arrest that persisted for at least 24 h post-irradiation, promoting apoptotic cell death in a large proportion of cells. CONCLUSION: Our findings demonstrate that the radiosensitising effect of 2-DG was significantly enhanced by its combination with metformin. This clearly demonstrates that dual metabolic targeting has potential to improve clinical outcomes in children with high-risk neuroblastoma by overcoming radioresistance.

11.
Oncology (Williston Park) ; 34(9): 370-376, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-1231670

ABSTRACT

In an asymptomatic 77-yearold woman, former 55 packyears smoker, a routine X-ray showed a 45-mm superior left lobe lesion. A chest CT scan confirmed a 36-mm superior left lobe lesion and an aortic-pulmonary lymph node enlargement measuring 42 mm, suspicious for neoplasia. A PET-CT scan showed an elevated uptake in the primary lesion, in the aortic-pulmonary lymph node, and in the left hilar lymph node with a standardized uptake value - 40 and 4.3, respectively. CT-guided lung biopsy showed a lung squamous cell carcinoma. An endobronchial ultrasound-guided transbronchial needle aspiration for lymph-node staging was negative for lymph node spread. Brain MRI was negative. Final staging was determined to be a IIIA (T2bN2) squamous cell carcinoma of the lung.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Squamous Cell/therapy , Coronavirus Infections/diagnosis , Lung Neoplasms/therapy , Pneumonia, Viral/diagnosis , Pneumonia/diagnosis , Aged , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Betacoronavirus , COVID-19 , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/diagnostic imaging , Chemoradiotherapy , Consolidation Chemotherapy , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Paclitaxel/administration & dosage , Pandemics , Pneumonia/chemically induced , SARS-CoV-2
12.
J Immunother Cancer ; 9(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1228897

ABSTRACT

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Immunotherapy/methods , Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , Cytokine Release Syndrome/pathology , Humans , Immunization, Passive/methods , Immunotherapy/adverse effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-1beta/blood , Interleukin-6/blood , Nitriles , Pyrazoles/therapeutic use , Pyrimidines , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Tumor Necrosis Factor-alpha/blood
13.
Res Social Adm Pharm ; 18(3): 2524-2528, 2022 03.
Article in English | MEDLINE | ID: covidwho-1228159

ABSTRACT

The COVID-19 pandemic has met international health systems with a low level of preparedness and emergency response. While the emergence of effective vaccines has offered the Governments, scientific communities, and members of the public a possible way out of the pandemic, effective pharmacotherapy, including immunotherapy for COVID-19 prevention and treatment, are yet to be established. Internationally, this has led to a surge in the demand and supply of many complementary and alternative medicines (CAM) and practices. Recent studies have shown increasing CAM information requests made to pharmacists and other healthcare staff from members of public and patients aimed at prevention, symptoms relief or treatment of COVID-19. In this context, it is imperative that healthcare professionals, including pharmacists, are acquainted with current practices, policies, and research in relation to CAM use in COVID-19. This narrative commentary will provide an update on global practices, policies and research in regards to CAM use in the context of COVID-19. Healthcare professionals' understanding of popular CAMs and those tipped for potential benefits in COVID-19, patient and consumer behaviors in relation to CAM use; and healthcare professionals' awareness of cultural, religious, and self-care practices associated with CAM use are imperative to inform effective communication and counselling practices and promote evidence based self-care when patients present for advice. This narrative provides relevant discussions specific to different continents and regions historically linked to diverse CAM practices.


Subject(s)
COVID-19 , Complementary Therapies , Humans , Pandemics , Policy , SARS-CoV-2
14.
Hum Antibodies ; 29(3): 179-191, 2021.
Article in English | MEDLINE | ID: covidwho-1226968

ABSTRACT

The harmful COVID-19 pandemic caused by the SARS-CoV-2 coronavirus imposes the scientific community to develop or find conventional curative drugs, protective vaccines, or passive immune strategies rapidly and efficiently. Passive immunity is based on recovering hyper-immune plasma from convalescent patients, or monoclonal antibodies with elevated titer of neutralizing antibodies with high antiviral activity, that have potential for both treatment and prevention. In this review, we focused on researching the potentiality of monoclonal antibodies for the prevention and treatment of COVID-19 infection. Our research review includes antibody-based immunotherapy, using human monoclonal antibodies targeting SARS-CoV-2 viral protein regions, specifically the spike protein regions, and using hyper-immune plasma from convalescent COVID-19 patients, in which monoclonal antibodies act as immunotherapy for the cytokine storm syndrome associated with the COVID-19 infection. In addition, we will demonstrate the role of the monoclonal antibodies in the development of candidate vaccines for SARS-CoV-2. Moreover, the recent progress of the diagnostic mouse monoclonal antibodies' role will be highlighted, as an accurate and rapid diagnostic assay, in the antigen detection of SARS-CoV-2. In brief, the monoclonal antibodies are the potential counter measures that may control SARS-CoV-2, which causes COVID-19 disease, through immunotherapy and vaccine development, as well as viral detection.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/drug therapy , Immunization, Passive , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , COVID-19/immunology , Humans , Pandemics , SARS-CoV-2/immunology
15.
Lung Cancer ; 156: 147-150, 2021 06.
Article in English | MEDLINE | ID: covidwho-1219424

ABSTRACT

Durvalumab is the first approved adjuvant immunotherapy agent for patients with stage III NSCLC treated with concurrent chemoradiotherapy and is associated with improved overall survival. In order to minimise the number of hospital visits for patients receiving durvalumab during the COVID-19 pandemic we implemented 4-weekly (20 mg/kg) durvalumab in place of 2-weekly infusions at The Royal Marsden Hospital. We assessed the potential impact of the safety of a 4-weekly schedule in patients receiving adjuvant durvalumab. We carried out a retrospective study of 40 patients treated with 2-weekly and 4-weekly infusions of durvalumab prior to and during the COVID-19 pandemic. Clinical documentation was analysed from 216 consultations across 40 patients receiving 2-weekly durvalumab and 66 consultations of 14 patients who switched from 2-weekly to 4-weekly durvalumab during the COVID-19 pandemic. In patients receiving 2-weekly durvalumab, the rate of grade 3 and 4 toxicities was 15 % compared to 7% in patients receiving 4-weekly durvalumab. Pre-existing autoimmune disease was considered a risk factor for the development of grade 3 or 4 toxicities. We did not observe any difference in the rate of grade 1 and 2 toxicities between the two groups. Our findings support the use of 4-weekly durvalumab during the COVID-19 pandemic and beyond, obviating the need for 2-weekly face-to-face consultations and blood tests, relevant given the current pandemic and the need to re-structure cancer services to minimise patient hospital visits and exposure to SARS-CoV-2.


Subject(s)
COVID-19 , Lung Neoplasms , Antibodies, Monoclonal , Humans , Lung Neoplasms/drug therapy , Pandemics , Retrospective Studies , SARS-CoV-2
16.
J Oncol Pharm Pract ; 27(6): 1461-1467, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1218934

ABSTRACT

PURPOSE: We aimed to determine the COVID-19 infection rate and determine the factors that affect hospitalization and prognosis in patients receiving systemic chemotherapy (CT), immunotherapy (IT) and molecular-targeted therapies at our hospital within three months after the onset of COVID-19 pandemic. MATERIALS AND METHODS: The patients who received systemic treatment at chemotherapy unit with diagnosis of cancer between 11 March 2020 and 11 June 2020 were included. The clinical and demographic characteristics of patients, the systemic treatments that they received (CT, IT, targeted therapies), and the stage of disease were determined. For the parameters that affect the hospitalization of COVID-19 infected patients were also determined. RESULTS: Among 1149 patients with cancer, 84 of them were infected with COVID-19, and the median age of infected patients was 61.0 (IQR: 21-84) and 60.7% of them were male. As a subtype of cancers lung cancer was more frequent in the patients who infected with COVID compared with non-infected ones and the difference was statistically significant when the underlying malignities were compared (32.1% vs 19.0%, p = 0.031). The hospitalization rate and receiving COVID-19 treatment were more frequent in metastatic patients who were receiving palliative therapy, and the difference was statistically significant (p = 0.01, p = 0.03). In our study, infection rate was similar among patients treated with CT, IT and CT plus targeted therapy; however, fewer COVID-19 infections were seen at patients who received only targeted therapy. CONCLUSION: COVID-19 infection is more frequent in cancer patients and tends to be more severe in metastatic cancer patients receiving anticancer treatment, and the continuation of palliative cancer treatments in these patients may cause increased cancer and infection-related morbidity and mortality.


Subject(s)
COVID-19 , Coronavirus Infections , Neoplasms , COVID-19/drug therapy , Coronavirus Infections/epidemiology , Humans , Male , Neoplasms/drug therapy , Pandemics , SARS-CoV-2
17.
Cureus ; 13(4): e14303, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1217164

ABSTRACT

In this report, we present the case of a 66-year-old man who received local consolidation radiotherapy to the right lung and mediastinum for oligometastatic non-small cell lung cancer (NSCLC) following partial response to upfront chemoimmunotherapy. He continued with maintenance immunotherapy and was asymptomatic for eight months after completing radiation therapy. He then developed symptoms consistent with pneumonitis within three to five days of his first administration of the coronavirus disease 2019 (COVID-19) vaccine injection. He reported that these symptoms significantly intensified within three to five days of receiving his second dose of the vaccine. The clinical time frame and radiographic evidence raised suspicion for radiation recall pneumonitis (RRP). Patients undergoing maintenance immunotherapy after prior irradiation may be at increased risk of this phenomenon that may be triggered by the administration of the COVID-19 vaccine.

18.
Arch Virol ; 166(8): 2109-2117, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1216221

ABSTRACT

Millions of people across the globe have been affected by coronavirus disease 2019 (COVID-19), which began in Wuhan, China, and is caused by SARS-CoV-2. COVID-19 has a variety of clinical characteristics and triggers immune responses required for the elimination of the viral agent. Currently, no effective treatment options are available for targeting SARS-CoV-2 infection. Repurposing of drugs such as chloroquine, thalidomide, and leflunomide alongside convalescent plasma is being employed as a therapeutic strategy. Clinical studies have shown that both asymptomatic and symptomatic patients can have an extremely active immune response that is largely attributable to immune system modulations. This includes cytokine storm syndrome (CSS), which affects the adaptive immune system, leading to exhaustion of natural killer (NK) cells and thrombocytopenia in some cases. This review examines the interaction of SARS-CoV-2 with the host immune system and the potential for the development of appropriate immunotherapy for the treatment of COVID-19.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , CD8-Positive T-Lymphocytes/immunology , COVID-19/therapy , Cytokine Release Syndrome/immunology , Endoplasmic Reticulum Stress/immunology , Humans , Immunotherapy , Inflammation , Killer Cells, Natural/immunology , Thrombocytopenia/immunology
19.
J Immunother Cancer ; 9(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1209683

ABSTRACT

The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19.


Subject(s)
COVID-19/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Neoplasms/therapy , Pneumonia/immunology , SARS-CoV-2/immunology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Diagnosis, Differential , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunocompromised Host/immunology , Immunotherapy/adverse effects , Neoplasms/immunology , Pneumonia/chemically induced , Pneumonia/diagnosis , SARS-CoV-2/physiology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
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