Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer

被引：3

作者：

Chaib, Mehdi ^{[1
]}

Holt, Jeremiah R. ^{[2
]}

Fisher, Emilie L. ^{[3
,4
]}

Sipe, Laura M. ^{[2
,12
]}

Bohm, Margaret S. ^{[5
]}

Joseph, Sydney C. ^{[2
]}

Simmons, Boston W. ^{[2
]}

Eugin Simon, Samson ^{[2
]}

Yarbro, Johnathan R. ^{[2
]}

Tanveer, Ubaid ^{[2
]}

Halle, Jessica L. ^{[6
]}

Carson, James A. ^{[6
]}

Hollingsworth, T. J. ^{[5
,7
,8
]}

Wei, Qingqing ^{[9
]}

Rathmell, Jeffrey C. ^{[3
,4
]}

Thomas, Paul G. ^{[5
,10
]}

Hayes, D. Neil ^{[2
,11
]}

Makowski, Liza ^{[1
,2
,5
,11
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA

[2] Univ Tennessee, Coll Med, Dept Med, Div Hematol & Oncol,Hlth Sci Ctr, Memphis, TN 38163 USA

[3] Vanderbilt Univ Sch Med, Vanderbilt Ctr Immunobiol, Nashville, TN 37235 USA

[4] Vanderbilt Univ Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA

[5] Univ Tennessee, Coll Med, Dept Microbiol Immunol & Biochem, Hlth Sci Ctr, Memphis, TN 38163 USA

[6] Univ Tennessee, Hlth Sci Ctr, Coll Hlth Profess, Dept Phys Therapy, Memphis, TN 38163 USA

[7] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Hamilton Eye Inst,Coll Med, Memphis, TN 38163 USA

[8] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA

[9] Augusta Univ, Dept Cellular Biol & Anat, Augusta, GA 30912 USA

[10] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[11] Univ Tennessee, Hlth Sci Ctr, Coll Med, UTHSC Ctr Canc Res, Memphis, TN 38163 USA

[12] Univ Mary Washington, Coll Arts & Sci, Dept Biol Sci, Fredericksburg, VA 22401 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 51期

基金：

美国国家卫生研究院;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; MYELOID CELLS; BILE-ACIDS; ACTIVATION; INHIBITION; SET; POPULATIONS; RESISTANCE; MONOCYTES; TARGETS;

D O I：

10.1126/sciadv.add3231

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKC delta), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors. PKC delta(-/-) mice displayed reduced tumor progression compared to wild types, with increased response to anti-PD-1. Tumors from PKC delta(-/-) mice demonstrated TH1-skewed immune response including increased antigen presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in control but not PKC delta(-/-) mice. Coinjection of PKC delta(-/-) M2-like macrophages with cancer cells into wild-type mice markedly delayed tumor growth and significantly increased intratumoral T cell activation compared to PKC delta(+/+) controls. PKC delta deficiency reprogrammed MPs by activating type I and type II interferon signaling. Thus, PKC delta might be targeted to reprogram MPs to augment ICB efficacy.

引用

页数：15

共 84 条

[1] Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade [J].

Ajona, Daniel ;

Ortiz-Espinosa, Sergio ;

Lozano, Teresa ;

Exposito, Francisco ;

Calvo, Alfonso ;

Valencia, Karmele ;

Redrado, Miriam ;

Remirez, Ana ;

Lecanda, Fernando ;

Alignani, Diego ;

Lasarte, Juan J. ;

Macaya, Irati ;

Senent, Yaiza ;

Bertolo, Cristina ;

Sainz, Cristina ;

Gil-Bazo, Ignacio ;

Eguren-Santamaria, Inaki ;

Lopez-Picazo, Jose M. ;

Gonzalez, Alvaro ;

Perez-Gracia, Jose L. ;

de Andrea, Carlos E. ;

Vicent, Silvestre ;

Sanmamed, Miguel F. ;

Montuenga, Luis M. ;

Pio, Ruben .

NATURE CANCER, 2020, 1 (01) :75-+

[2] TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy [J].

Akalu, Yemsratch T. ;

Rothlin, Carla V. ;

Ghosh, Sourav .

IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :165-177

[3] Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway [J].

Alicea-Torres, Kevin ;

Sanseviero, Emilio ;

Gui, Jun ;

Chen, Jinyun ;

Veglia, Filippo ;

Yu, Qiujin ;

Donthireddy, Laxminarasimha ;

Kossenkov, Andrew ;

Lin, Cindy ;

Fu, Shuyu ;

Mulligan, Charles ;

Nam, Brian ;

Masters, Gregory ;

Denstman, Fred ;

Bennett, Joseph ;

Hockstein, Neil ;

Rynda-Apple, Agnieszka ;

Nefedova, Yulia ;

Fuchs, Serge Y. ;

Gabrilovich, Dmitry, I .

NATURE COMMUNICATIONS, 2021, 12 (01)

[4] Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma [J].

Bi, Kevin ;

He, Meng Xiao ;

Bakouny, Ziad ;

Kanodia, Abhay ;

Napolitano, Sara ;

Wu, Jingyi ;

Grimaldi, Grace ;

Braun, David A. ;

Cuoco, Michael S. ;

Mayorga, Angie ;

DelloStritto, Laura ;

Bouchard, Gabrielle ;

Steinharter, John ;

Tewari, Alok K. ;

Vokes, Natalie, I ;

Shannon, Erin ;

Sun, Maxine ;

Park, Jihye ;

Chang, Steven L. ;

McGregor, Bradley A. ;

Haq, Rizwan ;

Denize, Thomas ;

Signoretti, Sabina ;

Guerriero, Jennifer L. ;

Vigneau, Sebastien ;

Rozenblatt-Rosen, Orit ;

Rotem, Asaf ;

Regev, Aviv ;

Choueiri, Toni K. ;

Van Allen, Eliezer M. .

CANCER CELL, 2021, 39 (05) :649-+

[5] Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity [J].

Binnewies, Mikhail ;

Mujal, Adriana M. ;

Pollack, Joshua L. ;

Combes, Alexis J. ;

Hardison, Emily A. ;

Barry, Kevin C. ;

Tsui, Jessica ;

Ruhland, Megan K. ;

Kersten, Kelly ;

Abushawish, Marwan A. ;

Spasic, Marko ;

Giurintano, Jonathan P. ;

Chan, Vincent ;

Daud, Adil, I ;

Ha, Patrick ;

Ye, Chun J. ;

Roberts, Edward W. ;

Krummel, Matthew F. .

CELL, 2019, 177 (03) :556-+

[6] Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity [J].

Broz, Miranda L. ;

Binnewies, Mikhail ;

Boldajipour, Bijan ;

Nelson, Amanda E. ;

Pollack, Joshua L. ;

Erle, David J. ;

Barczak, Andrea ;

Rosenblum, Michael D. ;

Daud, Adil ;

Barber, Diane L. ;

Amigorena, Sebastian ;

van't Veer, Laura J. ;

Sperling, Anne I. ;

Wolf, Denise M. ;

Krummel, Matthew F. .

CANCER CELL, 2014, 26 (05) :638-652

[7] The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy [J].

Bruni, Daniela ;

Angell, Helen K. ;

Galon, Jerome .

NATURE REVIEWS CANCER, 2020, 20 (11) :662-680

[8] The Gene Ontology resource: enriching a GOld mine [J].

Carbon, Seth ;

Douglass, Eric ;

Good, Benjamin M. ;

Unni, Deepak R. ;

Harris, Nomi L. ;

Mungall, Christopher J. ;

Basu, Siddartha ;

Chisholm, Rex L. ;

Dodson, Robert J. ;

Hartline, Eric ;

Fey, Petra ;

Thomas, Paul D. ;

Albou, Laurent-Philippe ;

Ebert, Dustin ;

Kesling, Michael J. ;

Mi, Huaiyu ;

Muruganujan, Anushya ;

Huang, Xiaosong ;

Mushayahama, Tremayne ;

LaBonte, Sandra A. ;

Siegele, Deborah A. ;

Antonazzo, Giulia ;

Attrill, Helen ;

Brown, Nick H. ;

Garapati, Phani ;

Marygold, Steven J. ;

Trovisco, Vitor ;

Dos Santos, Gil ;

Falls, Kathleen ;

Tabone, Christopher ;

Zhou, Pinglei ;

Goodman, Joshua L. ;

Strelets, Victor B. ;

Thurmond, Jim ;

Garmiri, Penelope ;

Ishtiaq, Rizwan ;

Rodriguez-Lopez, Milagros ;

Acencio, Marcio L. ;

Kuiper, Martin ;

Laegreid, Astrid ;

Logie, Colin ;

Lovering, Ruth C. ;

Kramarz, Barbara ;

Saverimuttu, Shirin C. C. ;

Pinheiro, Sandra M. ;

Gunn, Heather ;

Su, Renzhi ;

Thurlow, Katherine E. ;

Chibucos, Marcus ;

Giglio, Michelle .

NUCLEIC ACIDS RESEARCH, 2021, 49 (D1) :D325-D334

[9] Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells [J].

Casanova-Acebes, Maria ;

Dalla, Erica ;

Leader, Andrew M. ;

LeBerichel, Jessica ;

Nikolic, Jovan ;

Morales, Blanca M. ;

Brown, Markus ;

Chang, Christie ;

Troncoso, Leanna ;

Chen, Steven T. ;

Sastre-Perona, Ana ;

Park, Matthew D. ;

Tabachnikova, Alexandra ;

Dhainaut, Maxime ;

Hamon, Pauline ;

Maier, Barbara ;

Sawai, Catherine M. ;

Agullo-Pascual, Esperanza ;

Schober, Markus ;

Brown, Brian D. ;

Reizis, Boris ;

Marron, Thomas ;

Kenigsberg, Ephraim ;

Moussion, Christine ;

Benaroch, Philippe ;

Aguirre-Ghiso, Julio A. ;

Merad, Miriam .

NATURE, 2021, 595 (7868) :578-+

[10] Myeloid cells in the era of cancer immunotherapy: Top 3 unanswered questions [J].

Chaib, Mehdi ;

Tanveer, Ubaid A. ;

Makowski, Liza .

PHARMACOLOGY & THERAPEUTICS, 2023, 244

← 1 2 3 4 5 6 7 8 9 →