|Table of Contents|

Role of PD-1/PD-L1 pathway,Th17 and Tregs cells in tumor immunity

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 18
Page:
3519-3523
Research Field:
Publishing date:

Info

Title:
Role of PD-1/PD-L1 pathway,Th17 and Tregs cells in tumor immunity
Author(s):
ZHANG LanfangZHANG MingjuanXU JinxiuLI ShanCHEN YuWANG WenjingYANG JuntianLI ShengyunGU Meiling
Cancer Medical Center,Weihai Municipal Hospital,Shandong University,Shandong Weihai 264200,China.
Keywords:
tumorPD-1/PD-L1Th17Tregs
PACS:
R730.51
DOI:
10.3969/j.issn.1672-4992.2023.18.035
Abstract:
Tumor immunotherapy,especially PD-1/PD-L1 immunosuppressive checkpoint inhibitors,has become an important part of tumor treatment strategy in the past decade.The blocking of PD-1/PD-L1 signaling pathway relieves the inhibition of PD-1 pathway on T cells,promotes the attack of activated T cells on tumor cells,and has advantages in prolonging the remission period of tumor.PD-1/PD-L1 immunotherapy is effective in the treatment of solid malignant tumor,but it also has some shortcomings,which is related to the complexity of tumor microenvironment.Tregs and Th17 cells play an important role in tumor microenvironment and are closely related to the occurrence and development of tumors.However,the complicated relationship between PD-1/PD-L1 pathway,Tregs,and Th17 cells has not been fully clarified.Here,we summarized the immunoregulation mechanisms and discussed the crosstalk in PD-1/PD-L1 pathway,Tregs and Th17 cells,hoping to provide novel insights for the future cancer treatment.

References:

[1] PEARCE H,CROFT W,NICOL SM,et al .Tissue-resident memory T cells in pancreatic ductal adenocarcinoma coexpress PD-1 and TIGIT and functional inhibition is reversible by dual antibody blockade[J].Cancer Immunol Res,2023,11(4):435-449.
[2] TICHET M,WULLSCHLEGER S,CHRYPLEWICZ A,et al.Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages[J].Immunity,2023,56(1):162-179.
[3] ISHIDA Y,AGATA Y,SHIBAHARA K,et al.Induced expression of PD-1,a novel member of the immunoglobulin gene superfamily,upon programmed cell death[J].EMBO J,1992,11:3887-3895.
[4] SUH WK,TAFURI A,BERG-BROWN NN,et al.The inducible costimulator plays the major costimulatory role in humoral immune responses in the absence of CD28[J].J Immunol,2004,172:5917-5923.
[5] KEIR ME,BUTTE MJ,FREEMAN GJ,et al.PD-1 and its ligands in tolerance and immunity[J].Annu Rev Immunol,2008,26:677-704.
[6] JIANG X,WANG J,DENG X,et al.Role of the tumor microenvironment in PDL1/PD-1-mediated tumor immune escape[J].Mol Cancer,2019,18(1):10.
[7] ZHANG X,SCHWARTZ JC,GUO X,et al.Structural and functional analysis of the costimulatory receptor programmed death-1[J].Immunity,2004,20(3):337-347.
[8] HOFMEYER KA,JEON H,ZANG X.The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T lymphocyte exhaustion[J].J Biomed Biotechnol,2011,2011:451694.
[9] PATSOUKIS N,BROWN J,PETKOVA V,et al.Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation[J].Sci Signal,2012,5(230):ra46.
[10] NICHOLAS KJ,ZERN EK,BARNETT L,et al.B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade[J].PLoS One,2013,8(12):e84185.
[11] KATAOKA K,SHIRAISHI Y,TAKEDA Y,et al.Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers[J].Nature,2016,534:402-406.
[12] SKOULIDIS F,BYERS LA,DIAO L,et al.Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology,immune profiles,and therapeutic vulnerabilities[J].Cancer Discov,2015,5:860-877.
[13] LASTWIKA KJ,WILSON W,LI QK,et al.Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer[J].Cancer Res,2016,76:227-238.
[14] RIBAS A.Adaptive immune resistance:how cancer protects from immune attack[J].Cancer Discov,2015,5:915-919.
[15] OKIYAMA N,KATZ SI.Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes[J].J Autoimmun,2014,53:1-9.
[16] SPRANGER S,KOBLISH HK,HORTON B,et al.Mechanism of tumor rejection with doublets of CTLA-4,PD-1/PD-L1,or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment[J].J Immunother Cancer,2014,2:3.
[17] GERSHON RK,KONDO K.Cell interactions in the induction of tolerance:the role of thymic lymphocytes[J].Immunology,1970,18:723.
[18] SAKAGUCHI S,SAKAGUCHI N,ASANO M,et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J].J Immunol,1995,155:1151-1164.
[19] GIANCHECCHI E,FIERABRACCI A.Inhibitory receptors and pathways of lymphocytes:the role of PD-1 in Treg development and their involvement in autoimmunity onset and cancer progression[J].Front Immunol,2018,9:2374.
[20] BOYMAN O,SPRENT J.The role of interleukin-2 during homeostasis and activation of the immune system[J].Nat Rev Immunol,2012,12(3):180-190.
[21] MALCHOW S,LEVENTHAL DS,NISHI S,et al.Aire-dependent thymic development of tumor-associated regulatory T cells[J].Science,2013,339(6124):1219-1224.
[22] SAKAGUCHI S,WING K,ONISHI Y,et al.Regulatory T cells:how do they suppress immune responses[J] Int Immunol,2009,21:1105-1111.
[23] VON BOEHMER H,DANIEL C.Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer[J].Nat Rev Drug Discov,2013,12:51-63.
[24] CHAUDHARY B,ELKORD E.Regulatory T cells in the tumor microenvironment and cancer progression:role and therapeutic targeting[J].Vaccines,2016,4:1-25.
[25] WARD ST,LI KK,HEPBURN E,et al.The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer[J].Br J Cancer,2015,112:319-328.
[26] LIU C,WORKMAN CJ,VIGNALI DA.Targeting regulatory T cells in tumors[J].FEBS J,2016,283:2731-2748.
[27]DUHEN R,FESNEAU O,SAMSON KA,et al.PD-1 and ICOS coexpression identifies tumor-reactive CD4+ T cells in human solid tumors[J].J Clin Investig,2022,132:e156821.
[28] SIMPSON TR,LI F,MONTALVO-ORTIZ W,et al.Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma[J].J Exp Med,2013,210:1695-710.
[29] AKEUS P,LANGENES V,KRISTENSEN J,et al.Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+) conventional T cells in intestinal tumors[J].Eur J Immunol,2015,45:1654-1666.
[30] LEE Y,AWASTHI A,YOSEF N,et al.Induction andmolecular signature of pathogenic TH17 cells[J].Nat Immunol,2012,13:991-999.
[31] GU C,WU L,LI X.IL-17 family:cytokines,receptors and signaling[J].Cytokine,2013,64:477-485.
[32] MURUGAIYAN G,SAHA B.Protumor vs antitumor functions of IL-17[J].J Immunol,2009,183:4169-4175.
[33] MARTIN-OROZCO N,MURANSKI P,CHUNG Y,et al.T helper 17 cells promote cytotoxic T cell activation in tumor immunity[J].Immunity,2009,31:787-798.
[34] ANKATHATTI MUNEGOWDA M,DENG Y,MULLIGAN SJ,et al.Th17 and Th17-stimulated CD8+ T cells play a distinct role in Th17-induced preventive and therapeutic antitumor immunity[J].Cancer Immunol Immunother,2011,60:1473-1484.
[35] QIAN X,CHEN H,WU X,et al.Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis[J].Cytokine,2017,89:34-44.
[36] KNOCHELMANN HM,DWYER CJ,BAILEY SR,et al.When worlds collide:Th17 and Treg cells in cancer and autoimmunity[J].Cell Mol Immunol,2018,15:458-469.
[37] GNERLICH JL,MITCHEM JB,WEIR JS,et al.Induction of Th17 cells in the tumor microenvironment improves overall survival in a murine model of pancreatic cancer[J].J Immunol,2010,185:4063-4071.
[38] CANTINI G, PISATI F, MASTROPIETRO A, et al. A critical role for regulatory T cells in driving cytokine profiles of Th17 cells and their modulation of glioma microenvironment[J]. Cancer Immunol Immunother,2011,60:1739-1750.
[39] BOUTROS C,TARHINI A,ROUTIER E,et al.Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination[J].Nat Rev Clin Oncol,2016,13:473-486.
[40] MENZIES AM,JOHNSON DB,RAMANUJAM S,et al.Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab[J].Ann Oncol,2016,28:368-376.
[41] PARK HJ,PARK JS,JEONG YH,et al.PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells[J].J Immunol,2015,194:5801-5811.
[42] FRANCISCO LM,SALINAS VH,BROWN KE,et al.PD-L1 regulates the development,maintenance,and function of induced regulatory T cells[J].J Exp Med,2009,206:3015-3029.
[43] KOS K,SALVAGNO C,WELLENSTEIN MD,et al.Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling[J].Oncoimmunology,2022,11(1):2063225.
[44] HONG G,SUN P,CHUNG C,et al.Plasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer[J].J Cancer Res Clin Oncol,2023,149(1):159-171.
[45] MISPELBAUM R,HATTENHAUER ST,HELD SAE,et al.Baseline immune signature score of Tregs×HLA-DR+CD4+ T cells×PD1+CD8+ T cells predicts outcome to immunotherapy in cancer patients[J].Front Immunol,2022,13:1054161.
[46] PALOMERO J,PANISELLO C,LOZANO-RABELLA M,et al.Biomarkers of tumor-reactive CD4+ and CD8+ TILs associate with improved prognosis in endometrial cancer[J].J Immunother Cancer,2022,10(12):e005443.
[47] BASDEO SA,CLUXTON,DEBORAH,et al.Ex-Th17 (Nonclassical Th1) cells are functionally distinct from classical Th1 and Th17 cells and are not constrained by regulatory T cells[J].J Immunol,2017,198:2249-2259.
[48] ESFAHANI K,MILLER W.Reversal of autoimmune toxicity and loss of tumorresponse by interleukin-17 blockade[J].N Engl J Med,2017,376:1989-1991.
[49] KRIEG C,NOWICKA M,GUGLIETTA S,et al.High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy[J].Nat Med,2018,24(2):144-153.

Memo

Memo:
-
Last Update: 1900-01-01