MSGID: 1:317/3 64a643ab   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    A two-for-one approach to boost melanoma immunotherapy    
    One protein could help scientists fight treatment-resistant melanoma from   
   all directions.    
      
     Date:   
         July 5, 2023   
     Source:   
         Sanford Burnham Prebys   
     Summary:   
         New research has helped explain how melanoma evades the immune   
         system and may guide the discovery of future therapies for the   
         disease.   
      
      
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   New research from Sanford Burnham Prebys has helped explain how melanoma   
   evades the immune system and may guide the discovery of future therapies   
   for the disease. The study found that a protein known to be active in   
   immune cells is also active inside melanoma cells, helping promote tumor   
   growth. The findings, published in the journal Science Advances, suggest   
   that targeting this protein with new drugs may deliver a powerful double   
   hit to melanoma tumors.   
      
   "The immune system's control of a tumor is influenced by both internal   
   factors within tumor cells, as well as factors from the tumor's   
   surroundings," says first author Hyungsoo Kim, Ph.D., a research assistant   
   professor at Sanford Burnham Prebys in the lab of senior author Ze'ev   
   Ronai, Ph.D. "We found that the protein we're studying is involved in   
   both, which makes it an ideal target for new cancer therapies."  One of   
   the most significant breakthroughs in cancer therapy in the last century   
   is the development of immunotherapy, an approach that helps improve the   
   immune system's ability to fight cancer on its own without the use of   
   toxic chemotherapy drugs.   
      
   "Immunotherapy is the first-line therapy for several cancers now, but the   
   success of immunotherapy is limited because many cancers either don't   
   respond to it or become resistant over time," says Kim. "An important   
   goal remains to improve the effectiveness of immunotherapy."  To find   
   ways to boost immunotherapy in melanoma, the research team analyzed data   
   from patient tumors to identify genes that may coincide with patients'   
   responsiveness to immunotherapy. This led to the identification of a   
   protein that helps tumors evade the immune system -- called NR2F6 --   
   which was found not only in tumor cells, but also in the surrounding   
   noncancerous cells.   
      
   "Often we find that a protein has the opposite effect outside of tumors   
   compared to what it does within a tumor, which is less effective for   
   therapy," says Kim. "In the case of NR2F6, we found that it elicits the   
   same change in the tumor and in its surrounding tissues, pointing to a   
   synergistic effect.   
      
   This means that treatments that block this protein's activity   
   could be twice as effective."  To confirm their findings in mice,   
   the researchers genetically removed the NR2F6 protein in both melanoma   
   tumors and in the tumors' environment. This inhibited melanoma growth more   
   strongly, compared to when this effect occurs in either the tumor or its   
   microenvironment alone. The cancer's response to immunotherapy was also   
   enhanced upon loss of NR2F6 in both tumors and their microenvironment.   
      
   "This tells us that NR2F6 helps melanoma evade the immune system, and   
   without it, the immune system can more readily suppress tumor growth,"   
   adds Kim.   
      
   To help advance their discovery further, the team is working with the   
   Institute's Conrad Prebys Center for Chemical Genomics to identify new   
   drugs that can target NR2F6.   
      
   "Discovering drugs that can target this protein are expected to offer   
   a new way to treat melanomas, and possibly other tumors, that would   
   otherwise resist immunotherapy," says Kim.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Skin_Cancer # Brain_Tumor # Cancer # Immune_System #   
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             o Malignant_melanoma o Immune_system o Guide_dog o   
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   Journal Reference:   
      1. Hyungsoo Kim, Yongmei Feng, Rabi Murad, Joanna Pozniak, Carl   
      Pelz, Yeqing   
         Chen, Bhavik Dalal, Rosalie Sears, Eduard Sergienko,   
         Michael Jackson, Eytan Ruppin, Meenhard Herlyn, Curtis Harris,   
         Jean-Christophe Marine, Victoria Klepsch, Gottfried Baier, Ze'ev   
         A. Ronai. Melanoma-intrinsic NR2F6 activity regulates antitumor   
         immunity. Science Advances, 2023; 9 (27) DOI: 10.1126/sciadv.adf6621   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230705142949.htm   
      
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