Immune modulations of the tumor microenvironment in response to phototherapy

The tumor microenvironment(TME)promotes pro-tumor and anti-infammatory metabolismsand suppresses the host immune system.It prevents immune cells from fighting against cancereffectively,resulting in limited efficacy of many current cancer treatment modalities.Differenttherapies aim to overcome the immunosuppressive TME by combining various approaches tosynergize their effects for enhanced antitumor activity and augmented stimulation of the im-mune system.Immunotherapy has become a major therapeutic strategy because it unleashes thepower of the immune system by activating,enhancing,and directing immune responses to pre-vent,control,and eliminate cancer.Phototherapy uses light iradiation to induce tumor celldeath through photothermal,photochemical,and photo-immunological interactions.Photo-therapy induces tumor immunogenic cell death,which is a precursor and enhancer for anti-tumorimmunity.However,phototherapy alone has limited effects on long-term and systemic anti-tumor immune responses.Phototherapy can be combined with immunotherapy to improve thetumoricidal effect by killing target tumor cells,enhancing immune cell infiltration in tumors,andrewiring pathways in the TME from antinfammatory to pro-inflammatory.Phototherapy-enhanced immunotherapy triggers effective cooperation bet ween innate and adaptive immunities,specifically targeting the tumor cells,whether they are localized or distant.Herein,the successes and limitations of phototherapy combined with other cancer treatmentmodalities will be discussed.Specifically,we will review the symergistic effects of phototherapy combined with different cancer therapies on tumor elimination and remodeling of the immuno-suppressive TME.Overll,phototherapy,in combination with other therapeutic modalities,canestablish anti-tumor pro-infammatory phenotypes in activated tumor-infiltrating T cells andB cells and activate systemic anti-tumor immune responses.

Gold nanoparticles inhibit activation of cancer-associated fibroblasts by disrupting communication from tumor and microenvironmental cells

Cancer-associated fibroblasts(CAFs)are a major constituent of the tumor microenvironment(TME)and an important contributor to cancer progression and therapeutic resistance.Regulation of CAF activation is a promising strategy to influence cancer outcomes.Here,we report that ovarian cancer cells(OCs)and TME cells promote the activation of ovarian CAFs,whereas gold nanoparticles(GNPs)of 20 nm in diameter inhibit the activation,as demonstrated by the changes in cell morphology,migration,and molecular markers.GNPs exert the effect by altering the levels of multiple fibroblast activation or inactivation proteins,such as TGF-β1,PDGF,uPA and TSP1,secreted by OCs and TME cells.Thus,GNPs represent a potential tool to help understand multicellular communications existing in the TME as well as devise strategies to disrupt the communication.