Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition
AbstractImmune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however,> 60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line I CI or combination treatment, we tested 25 SNPs, associated with> 2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568—a risk variant for allergy, colitis and type 1 diabetes—was associated with increased anti-PD-1 response, with significance surpassing multiple testing adjustments (OR 0.2 6; 95% CI 0.12–0.53;p = 0.0002). This variant maps to a locus of established immune-related genes: IL2 and IL21. Our study provides first evidence that autoimmune genetic susceptibility may modulate ICI efficacy, suggesting that systematic testing of autoimmune risk loci could reveal personalized biomarkers of ICI r esponse.
Clinical Implications Bullying is an issue for food-allergic patients. Allergists may benefit from education and resources to recognize and address this problem. Language: en...
39 y/o with triple-negative breast cancer, 1.9 cm in size, had lumpectomy after neoadjuvant chemo which showed complete response. I'm treating whole breast to 42.6/16. Would anyone omit boost? Thanks.
Thereâs no doubt that the surgical robotics market is getting more crowded the competition is increasing. Intuitive Surgical, a pioneer in the space, is well aware of this fact and took steps this week to boost the da Vinci surgical robot. For an undisclosed sum, the Sunnyvale, CA-based company said it is acquiring the robotic endoscope portion of SchÃ¶lly Fiberopticâs business. SchÃ¶lly Fiberoptic is a player in the field of visualization systems for minimally invasive diagnostic and surgical applications, headquartered in Germany â and one of I...
Authors: Rustagi N, Pareek P, Verma M, Sharma PK Abstract Quality home-based care for patients with the end-stage disease is increasingly being preferred. Responding to disease associated symptoms and complications may pose an array of challenges in evolving palliative care systems, as no formal institutional mechanism exists to respond to patient and caregiver's wishes. Family and primary care physicians can play an instrumental role in such scenarios by bridging the gaps between cancer specialists and patient and caregivers expectations. PMID: 31304713 [PubMed - in process]
Alyssa Dyal was 23, a film student in Boston, fooling around with a guy she'd met on a dating app, when everything changed. Within months she was diagnosed with stage 4 breast cancer.
Authors: Licari A, Ciprandi R, Marseglia G, Ciprandi G PMID: 31305035 [PubMed - in process]
ConclusionIn conclusion, this study showed that Aloe vera extract and its active component aloin activated the Wnt/β-catenin pathway and inhibited the Notch pathway in the presence of Wnt3a. While another active component, aloesin, activated the Wnt/β-catenin pathway and inhibited the Notch signaling pathway independent of Wnt3a. Given that Wnt/β-catenin and Notch pathway are closely associated with the progression of CRC, these findings would be helpful to better understand the colonic carcinogenicity of Aloe vera.Graphical abstract
XPOVIO is a drug used to treat a form of blood cancer called multiple myeloma. It is to be used in combination with dexamethasone (a type of corticosteroid) in patients with no other treatment options whose cancer came back after, or did not respond to, at least four previous treatments.
Carcinosarcomas are rare malignant tumors derived of both epithelial and mesenchymal elements. Herein, we report an elderly man originally diagnosed with a squamous cell carcinoma of the hand. Upon excision, the tumor was found to be a more aggressive carcinosarcoma. Immunohistochemical stains revealed that the sarcoma component of the lesion was vimentin positive, whereas the primary carcinoma tumor cells were positive for p63 and CK903. Both components were negative for CD34 and D2-40. This tumor was found to have angiolymphatic invasion and eventually metastasized to the axillary lymph nodes and lungs.
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...