b03ae19d7614d97842cd33cf186bb0a1 pmc_32630618.pdf f3f2bc08730bc5e77c9c0c46917383a5c0073991 pmc_32630618.pdf 93ac9951884d8a536670ff9257e8efc542cc61c7dba064b5ed3a603ebcc3adea pmc_32630618.pdf Title: Tumor Cell-Intrinsic Immunometabolism and Precision Nutrition in Cancer Immunotherapy Subject: One of the greatest challenges in the cancer immunotherapy field is the need to biologically rationalize and broaden the clinical utility of immune checkpoint inhibitors (ICIs). The balance between metabolism and immune response has critical implications for overcoming the major weaknesses of ICIs, including their lack of universality and durability. The last decade has seen tremendous advances in understanding how the immune system’s ability to kill tumor cells requires the conspicuous metabolic specialization of T-cells. We have learned that cancer cell-associated metabolic activities trigger shifts in the abundance of some metabolites with immunosuppressory roles in the tumor microenvironment. Yet very little is known about the tumor cell-intrinsic metabolic traits that control the immune checkpoint contexture in cancer cells. Likewise, we lack a comprehensive understanding of how systemic metabolic perturbations in response to dietary interventions can reprogram the immune checkpoint landscape of tumor cells. We here review state-of-the-art molecular- and functional-level interrogation approaches to uncover how cell-autonomous metabolic traits and diet-mediated changes in nutrient availability and utilization might delineate new cancer cell-intrinsic metabolic dependencies of tumor immunogenicity. We propose that clinical monitoring and in-depth molecular evaluation of the cancer cell-intrinsic metabolic traits involved in primary, adaptive, and acquired resistance to cancer immunotherapy can provide the basis for improvements in therapeutic responses to ICIs. Overall, these approaches might guide the use of metabolic therapeutics and dietary approaches as novel strategies to broaden the spectrum of cancer patients and indications that can be effectively treated with ICI-based cancer immunotherapy. Keywords: immune checkpoints; immune checkpoint inhibitors; metabolism; nutrition; diet Author: Elisabet Cuyàs, Sara Verdura, Begoña Martin-Castillo, Tomás Alarcón, Ruth Lupu, Joaquim Bosch-Barrera and Javier A. 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TrueType Identity-H yes yes yes 654 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:42:12 CEST RepresentationInformation: pmc_32630618.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:46:55 CEST Size: 2954033 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 5 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きづぴちぢはぬどっぜ〴ぜ〰うふのっぴどはのびぜ〴ぜ〰はてぜ〴ぜ〰ぉねねふのづぜ〴ぜ〰ぃとづっにばはどのぴびぜ〴ぜ〰ちのつぜ〴ぜ〰ぴとづぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰ぎちぴふひづぜ〴ぜ〰はてぜ〴ぜ〰ぉねねふのはびふばばひづびびどぶづぜ〴ぜ〰ごきぅ〺ぜ〴ぜ〰あちぴぴぬどのでぜ〴ぜ〰はぶづひぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰げづびはふひっづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰きづぴちぢはぬどっぜ〴ぜ〰いひふでびぜ〴ぜ〰ごちひでづぴどのでぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはびふばばひづびびどぶづぜ〴ぜ〰ぎちぴふひづぜ〴ぜ〰はてぜ〴ぜ〰ごきぅ〺ぜ〴ぜ〰ぁぜ〴ぜ〰うどひびぴ〭どの〭ぃぬちびびぜ〴ぜ〰こふっっづびびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰きづぴちぢはぬどびねぜ〴ぜ〰ぐどばづぬどのづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸱ Children: Item: Title: きづぴちぢはぬどっぜ〴ぜ〰いひふでびぜ〴ぜ〰ごちひでづぴどのでぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはびふばばひづびびどぶづぜ〴ぜ〰ぎちぴふひづぜ〴ぜ〰はてぜ〴ぜ〰ごきぅ〺ぜ〴ぜ〰ぁぜ〴ぜ〰うどひびぴ〭どの〭ぃぬちびびぜ〴ぜ〰こふっっづびびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰きづぴちぢはぬどびねぜ〴ぜ〰ぐどばづぬどのづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸱ Children: Item: Title: ぐとはびばとちぴどつべぬどのはびどぴはぬぜ〴ぜ〰〳〭かどのちびづぜ〴ぜ〰ぜ〵ぜ〰ぐぉ〳かぜ〵ㅜ〰ぜ〴ぜ〰ぉのとどぢどぴはひびぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰こどでのちぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸲ Item: Title: ぉいくぜ〴ぜ〰ぉのとどぢどぴはひびぜ〴ぜ〰ちのつぜ〴ぜ〰ぴとづぜ〴ぜ〰ごひべばはばとちの〭かべのふひづのどのづぜ〴ぜ〰ぐちぴとぷちべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰いどづぴちひべぜ〴ぜ〰ぉのぴづひぶづのぴどはのび〯きはつどてどっちぴどはのびぜ〴ぜ〰ぉねばちっぴどのでぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはびふばばひづびびどぶづぜ〴ぜ〰ごひちどぴびぜ〴ぜ〰はてぜ〴ぜ〰ごきぅぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどづぴちひべぜ〴ぜ〰ぉのぴづひぶづのぴどはのび〯きはつどてどっちぴどはのびぜ〴ぜ〰ぉねばちっぴどのでぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはびふばばひづびびどぶづぜ〴ぜ〰ごひちどぴびぜ〴ぜ〰はてぜ〴ぜ〰ごきぅぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃづぬぬ〭ぉのぴひどのびどっぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰ごひちどぴびぜ〴ぜ〰ちのつぜ〴ぜ〰ごとづぜ〴ぜ〰ぉねねふのづぜ〴ぜ〰ぃとづっにばはどのぴぜ〴ぜ〰ぃはねばはびどぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぃづぬぬび〺ぜ〴ぜ〰ぁぜ〴ぜ〰うはひではぴぴづのぜ〴ぜ〰いどねづのびどはのぜ〴ぜ〰はてぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぉねねふのはねづぴちぢはぬどびねぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰えはぷぜ〴ぜ〰ぃちのぜ〴ぜ〰しづぜ〴ぜ〰ぅへちねどのづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぃづぬぬ〭ぁふぴはのはねはふびぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰いづばづのつづのっどづびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのづぜ〴ぜ〰ぃとづっにばはどのぴぜ〴ぜ〰がちのつびっちばづ〿ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰えはぷぜ〴ぜ〰ぃちのぜ〴ぜ〰しづぜ〴ぜ〰ぅへちねどのづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰いどづぴちひべぜ〴ぜ〰ぉのぴづひぶづのぴどはのびぜ〴ぜ〰はのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅててどっちっべぜ〴ぜ〰はてぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぉねねふのはぴとづひちばべ〿ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: えはぷぜ〴ぜ〰ぃちのぜ〴ぜ〰しづぜ〴ぜ〰ぅへちねどのづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぃづぬぬ〭ぁふぴはのはねはふびぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰いづばづのつづのっどづびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのづぜ〴ぜ〰ぃとづっにばはどのぴぜ〴ぜ〰がちのつびっちばづ〿ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰えはぷぜ〴ぜ〰ぃちのぜ〴ぜ〰しづぜ〴ぜ〰ぅへちねどのづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰いどづぴちひべぜ〴ぜ〰ぉのぴづひぶづのぴどはのびぜ〴ぜ〰はのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅててどっちっべぜ〴ぜ〰はてぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぉねねふのはぴとづひちばべ〿ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: えはぷぜ〴ぜ〰ぃちのぜ〴ぜ〰しづぜ〴ぜ〰ぅへちねどのづぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰いどづぴちひべぜ〴ぜ〰ぉのぴづひぶづのぴどはのびぜ〴ぜ〰はのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぅててどっちっべぜ〴ぜ〰はてぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぉねねふのはぴとづひちばべ〿ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃぬどのどっちぬぜ〴ぜ〰ちのつぜ〴ぜ〰きはぬづっふぬちひぜ〴ぜ〰きはのどぴはひどのでぜ〴ぜ〰はてぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぃづぬぬ〭ぉのぴひどのびどっぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰ぴはぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぉねねふのはぴとづひちばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぇちばびぜ〴ぜ〰ちのつぜ〴ぜ〰がどねどぴちぴどはのびぜ〴ぜ〰はてぜ〴ぜ〰ぉねねふのはぴとづひちばべ〭あははびぴどのでぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰ちのつぜ〴ぜ〰いどづぴちひべぜ〴ぜ〰ぁばばひはちっとづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸶ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸶ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ONPZLV+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 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