zithromax and Melanoma

Immunotherapy using checkpoint blockade (ICB) with antibodies such as anti-PD-1 has revolutionised the treatment of many cancers. Despite its use to treat COVID-19 patients and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, the effect of hydroxychloroquine (HCQ) on cancer immunotherapy has not been examined. In this study, remarkably, we find that HCQ alone, or in combination with azithromycin (AZ), at doses used to treat patients, decreased the therapeutic benefit of anti-PD-1 in cancer immunotherapy. No deleterious effect was seen on untreated tumors. Mechanistically, HCQ and HCQ/AZ inhibited PD-L1 expression on tumor cells, while specifically targeting the anti-PD-1 induced increase in progenitor CD8+CD44+PD-1+TCF1+ tumor infiltrating T cells (TILs) and the generation of CD8+CD44+PD-1+ effectors. Surprisingly, it also impaired the appearance of a subset of terminally exhausted CD8+ TILs. No effect was seen on the presence of CD4+ T cells, FoxP3+ regulatory T cells (Tregs), thymic subsets, B cells, antibody production, myeloid cells, or the vasculature of mice. This study indicates for the first time that HCQ and HCQ/AZ negatively impact the ability of anti-PD-1 checkpoint blockade to promote tumor rejection.

Topics: Animals; Azithromycin; Cell Line, Tumor; Drug Antagonism; Hydroxychloroquine; Immune Checkpoint Inhibitors; Immunotherapy; Melanoma; Mice; Programmed Cell Death 1 Receptor; T-Lymphocytes

Outbreak of the new type coronavirus infection, known as coronavirus infection 2019 (COVID-19), has begun in December 2019, in Wuhan, China. As of today, 3 April 2020, 972,640 people affected and 50,325 people died from Severe Acute Respiratory Syndrome-Coronavirus 2. There is not any standard treatment for coronavirus infection 2019; however, there are promising data for hydroxychloroquine and some anti-retroviral drugs. Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) pathway is an important target for the cancer immunotherapy. However, there is a robust pre-clinical and clinical data regarding inhibitor effect of this pathway on the acute or chronic viral infections. Thus, blockade of this pathway may lead to an anti-viral effect and decrease viral load. Here, we report the clinical course of coronavirus infection 2019 infection of a patient in whom older aged, having multiple co-morbidities, and taking nivolumab for metastatic malignant melanoma. In contrast to her older age, comorbidities, and cancer diagnosis, she was in a good condition, and there was also no pneumonia finding. We think that this good clinical course of coronavirus infection 2019 infection may be related to blockade of PD-1/PDL-1 pathway with nivolumab. It is impossible to say that blockade of PD-1/PDL-1pathway is a treatment option for COVID-19; however, we want to share our experience.

Topics: Aged; Antineoplastic Agents, Immunological; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Hydroxychloroquine; Lung Neoplasms; Melanoma; Multiple Chronic Conditions; Nivolumab; Oseltamivir; Pandemics; Pneumonia, Viral; Programmed Cell Death 1 Receptor; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Treatment of malignancy with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors can cause mucocutaneous side effects resulting from T cell activation. Due to their recent development, the full side effect profile remains to be fully elucidated, however dermatologic adverse events are most common. The main oral toxicities of these immune checkpoint inhibitors include: xerostomia, dysgeusia, and lichenoid reactions. Oral mucositis occurs more rarely in the setting of PD-1 inhibition, and few other reports of a Grade 3 or higher, severe, stomatitis have been reported in the literature. We present a case of a 78-year-old woman with Grade 3 ulcerative oral mucositis that occurred 13 months after initiation of PD-1 inhibitor, pembrolizumab, for the treatment for lung adenocarcinoma. She was successfully treated with prednisone, and pembrolizumab was temporarily held by her oncologist. Physicians should be aware of the possibility of severe mucositis in the setting of PD-1 inhibitors, as well as the management. J Drugs Dermatol. 2018;17(7):807-809.

Topics: Adenocarcinoma; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Azithromycin; Female; Humans; Lung Neoplasms; Melanoma; Programmed Cell Death 1 Receptor; Severity of Illness Index; Stomatitis