MSGID: 1:317/3 649a6607   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Researchers uncover potential biomarkers of positive response to   
   immunotherapy    
    CXCL13-mediated recruitment of B cells could help predict response to   
   immunotherapy    
      
     Date:   
         June 26, 2023   
     Source:   
         University of California - Los Angeles Health Sciences   
     Summary:   
         Scientists have identified potential new biomarkers that could   
         indicate how someone diagnosed with metastatic melanoma will   
         respond to immunotherapy treatment.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
      
   ==========================================================================   
   FULL STORY   
   ==========================================================================   
   Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified   
   potential new biomarkers that could indicate how someone diagnosed with   
   metastatic melanoma will respond to immunotherapy treatment.   
      
   The researchers found when T cells are activated, they release a protein   
   called CXCL13, which helps attract more B cells and T cells to the tumor   
   site. The B cells then show the T cells specific parts of the tumor,   
   which leads to increased activation of the T cells and their ability   
   to fight the cancer. This cooperation between T cells and B cells was   
   associated with improved survival in patients diagnosed with metastatic   
   melanoma who were treated with immunotherapy, but not for those who   
   received targeted therapy (e.g., MEK inhibitors).   
      
   These findings could help guide new strategies to improve the   
   effectiveness of melanoma cancer treatments.   
      
   "Based upon our data, increased presence of B cells and CXCL13 protein in   
   the tumor after immunotherapy treatment may be predictive biomarkers for   
   durable immunotherapy response in melanoma patients and may be avenues   
   to enhance the response rate to immunotherapy in patients diagnosed   
   with melanoma," said co- senior author of the paper Willy Hugo, PhD,   
   assistant professor of Medicine in the division of Dermatology at the   
   David Geffen School of Medicine at UCLA and member of the UCLA Jonsson   
   Comprehensive Cancer Center. "For example, combination of anti-PD1   
   treatments with CXCL13 or B cell-directed therapies may be strategies   
   for patients who fail to respond to checkpoint immunotherapy alone."   
   Immune checkpoint inhibitors, which harness the body's immune system   
   to better attack cancer cells, have revolutionized the way people with   
   melanoma are treated. People with aggressive forms of the cancer are now   
   living longer, healthier lives. Despite the remarkable success of using   
   immune checkpoint inhibitors to treat people with advanced melanoma,   
   it is still difficult to predict who will benefit from the therapy.   
      
   Identifying mechanisms that determine how tumors can become resistant   
   to these therapies and understanding how to identify patients who will   
   and will not respond to them is critical to developing new and improved   
   treatments to help improve the response rate of these therapies.   
      
   To understand what may drive durable antitumor immune responses seen   
   with checkpoint immunotherapy in some melanoma patients, and why such   
   responses are less often seen in patients treated with other FDA-approved   
   targeted therapies, such as mutant BRAF and MEK inhibitors, the UCLA   
   team compared the immune responses induced by existing standard care   
   targeted and immunotherapies for people with metastatic melanoma.   
      
   The team completed a comparative genomics analysis using published   
   RNA-seq profiles of melanoma samples collected before and after either   
   therapy. They found that response to immunotherapy, but not targeted   
   therapy, is accompanied with significant infiltration of clonally diverse   
   B cells. The increase of B cell infiltration in response to immunotherapy   
   is accompanied by a significant upregulation of B-cell chemotactic factor,   
   CXCL13, by T cells.   
      
   "This study suggests that CXCL13 may play an important role in bringing   
   together T and B cells in the tumor microenvironment in patients who   
   respond to checkpoint immunotherapy, and that this cooperation may   
   be key to effective anti-tumor responses. Further studies are need to   
   determine if these pathways can be boosted in non-responders to improve   
   outcomes," said co-senior author of the paper Melissa Lechner, MD, PhD,   
   assistant professor of Medicine in the division of Endocrinology at the   
   David Geffen School of Medicine at UCLA and member of the UCLA Jonsson   
   Comprehensive Cancer Center.   
      
   These data also support a role for antigen presentation by B cells to   
   T cells in the tumor microenvironment, and highlight the potential of   
   using B cell- based cancer vaccines to enhance the effectiveness of   
   immune checkpoint immunotherapies.   
      
   The team now plans to further explore these mechanisms in preclinical   
   cancer models and test whether antigen presenting B cell and CXCL13   
   manipulation can improve anti-tumor immune responses in non-responders.   
      
   This work was supported in part by grants from the National Cancer   
   Institute (1R01CA236910) and a grant from Parker Institute for Cancer   
   Immunotherapy.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Skin_Cancer # Immune_System # Cancer # Brain_Tumor #   
                   Lymphoma # Lung_Cancer # Prostate_Cancer # Colon_Cancer   
       * RELATED_TERMS   
             o Malignant_melanoma o Rocky_Mountain_spotted_fever o   
             Delusions_of_parasite_infestation o Deep_brain_stimulation   
             o Brain_tumor o Hormone_replacement_therapy o   
             Calorie_restricted_diet o Stroke   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_Los_Angeles_Health_Sciences.   
      
   Original written by Denise Heady. Note: Content may be edited for style   
   and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Lizhong Ding, Lu Sun, Melissa T. Bu, Yanjun Zhang, Lauren N. Scott,   
         Robert M. Prins, Maureen A. Su, Melissa G. Lechner, Willy   
         Hugo. Antigen presentation by clonally diverse CXCR5+ B cells to   
         CD4 and CD8 T cells is associated with durable response to immune   
         checkpoint inhibitors.   
      
         Frontiers in Immunology, 2023; 14 DOI: 10.3389/fimmu.2023.1176994   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230626164211.htm   
      
   --- up 1 year, 17 weeks, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 218/700 226/30 227/114   
   SEEN-BY: 229/110 112 113 307 317 400 426 428 470 664 700 291/111 292/854   
   SEEN-BY: 298/25 305/3 317/3 320/219 396/45 5075/35   
   PATH: 317/3 229/426