Immune system-mediated tumor killing has revolutionized anti-tumor therapies, providing long-term and durable responses in some patients. The phosphoinositide 3-kinase (PI3K) pathway controls multiple biological processes and is frequently dysregulated in malignancies. Enormous efforts have been made to develop inhibitors against class I PI3K. Notably, with the increasing understanding of PI3K, it has been widely accepted that PI3K inhibition not only restrains tumor progression, but also reshapes the immunosuppressive tumor microenvironment. In this review, we focus on the pivotal roles of class I PI3Ks in adaptive and innate immune cells, as well as other stromal components. We discuss the modulation by PI3K inhibitors of the tumor-supportive microenvironment, including eliminating the regulatory immune cells, restoring cytotoxic cells or regulating angiogenesis. The potential combinations of PI3K inhibitors with other therapies to enhance the anti-tumor immunity are also described.
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Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606–19.
Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.
Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507.
Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015;15:7–24.
Robbins HL, Hague A. The PI3K/Akt pathway in tumors of endocrine tissues. Front Endocrinol. 2015;6:188.
Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, et al. Phosphatidylinositol-3-kinase as a therapeutic target in melanoma. Clin Cancer Res. 2009;15:3029.
Alzahrani AS. PI3K/Akt/mTOR inhibitors in cancer: at the bench and bedside. Semin Cancer Biol. 2019;59:125–32.
Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.
Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170:605–35.
Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol. 2013;31:675–704.
Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3:317–30.
So L, Fruman DA. PI3K signalling in B- and T-lymphocytes: new developments and therapeutic advances. Biochem J. 2012;442:465–81.
Suzuki H, Terauchi Y, Fujiwara M, Aizawa S, Yazaki Y, Kadowaki T, et al. Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase. Science. 1999;283:390–2.
Fruman DA, Snapper SB, Yballe CM, Davidson L, Yu JY, Alt FW, et al. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science. 1999;283:393–7.
Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, et al. Impaired B and T cell antigen receptor signaling in p110delta PI3-kinase mutant mice. Science. 2002;297:1031–4.
Jou ST, Carpino N, Takahashi Y, Piekorz R, Chao JR, Carpino N, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol. 2002;22:8580–91.
Wentink M, Dalm V, Lankester AC, van Schouwenburg PA, Scholvinck L, Kalina T, et al. Genetic defects in PI3Kdelta affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections. Clin Immunol. 2017;176:77–86.
Lougaris V, Faletra F, Lanzi G, Vozzi D, Marcuzzi A, Valencic E, et al. Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype. Clin Immunol. 2015;159:33–6.
Shiroki F, Matsuda S, Doi T, Fujiwara M, Mochizuki Y, Kadowaki T, et al. The p85alpha regulatory subunit of class IA phosphoinositide 3-kinase regulates beta-selection in thymocyte development. J Immunol. 2007;178:1349–56.
Janas ML, Varano G, Gudmundsson K, Noda M, Nagasawa T, Turner M. Thymic development beyond beta-selection requires phosphatidylinositol 3-kinase activation by CXCR4. J Exp Med. 2010;207:247–61.
Webb L., Vigorito E., Wymann M., Hirsch E., Turner M. Cutting edge: T cell development requires the combined activities of the p110γ and p110δ catalytic isoforms of phosphatidylinositol 3-kinase1. J Immunol. 2005;175:2783–7.
Swat W, Montgrain V, Doggett T, Douangpanya J, Puri K, Vermi W, et al. Essential role of PI3Kδ and PI3Kγ in thymocyte survival. Blood. 2006;107:2415–22.
Ward SG, Cantrell DA. Phosphoinositide 3-kinases in T lymphocyte activation. Curr Opin Immunol. 2001;13:332–8.
Okkenhaug K, Patton D, Bilancio A, Garcon F, Rowan W, Vanhaesebroeck B. The p110 isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol. 2006;177:5122–8.
Macintyre AN, Finlay D, Preston G, Sinclair LV, Waugh CM, Tamas P, et al. Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity. 2011;34:224–36.
Martin A, Schwartz M, Jameson S, Shimizu Y. Selective regulation of CD8 effector T cell migration by the p110γ isoform of phosphatidylinositol 3-kinase. J Immunol. 2008;180:2081–8.
Thomas MS, Mitchell JS, DeNucci CC, Martin AL, Shimizu Y. The p110gamma isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites. J Leukoc Biol. 2008;84:814–23.
McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, et al. CD4+CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002;16:311–23.
Lim EL, Okkenhaug K. PI3Kδ is a Treg target in cancer immunotherapy. Immunology. 2019;157:210–8.
Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. Inactivation of PI3K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014;510:407–11.
Dong S, Harrington BK, Hu EY, Greene JT, Lehman AM, Tran M, et al. PI3K p110δ inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression. J Clin Investig. 2018;129:122–36.
Hawkins PT, Stephens LR. PI3K signalling in inflammation. Biochim Biophys Acta. 2015;1851:882–97.
Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6:173–82.
Hirsch E, Katanaev V, Garlanda C, Azzolino O, Pirola L, Silengo L, et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science. 2000;287:1049–53.
Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science. 2000;287:1046–49.
Sasaki T, Irie-Sasaki J, Jones RG, Oliveira-dos-Santos AJ, Stanford WL, Bolon B, et al. Function of PI3Kγ in thymocyte development, T cell activation, and neutrophil migration. Science. 2000;287:1040.
Dahlgren C, Karlsson A. Respiratory burst in human neutrophils. J Immunol Methods. 1999;232:3–14.
Kulkarni S, Sitaru C, Jakus Z, Anderson KE, Damoulakis G, Davidson K, et al. PI3Kbeta plays a critical role in neutrophil activation by immune complexes. Sci Signal. 2011;4:ra23.
Mace E. Phosphoinositide-3-kinase signaling in human natural killer cells: new insights from primary immunodeficiency. Front Immunol. 2018;9:445.
Kerr WG, Colucci F. Inositol phospholipid signaling and the biology of natural killer cells. J Innate Immun. 2011;3:249–57.
Zebedin E, Simma O, Schuster C, Putz EM, Fajmann S, Warsch W, et al. Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance. Blood. 2008;112:4655–64.
Jiang K, Zhong B, Gilvary DL, Corliss BC, Hong-Geller E, Wei S, et al. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol. 2000;1:419–25.
al-Aoukaty A, Rolstad B, Maghazachi A. Recruitment of pleckstrin and phosphoinositide 3-kinase gamma into the cell membranes, and their association with G beta gamma after activation of NK cells with chemokines. J Immunol. 1999;162:3249–55.
Saudemont A, Garçon F, Yadi H, Roche-Molina M, Kim N, Segonds-Pichon A, et al. p110gamma and p110delta isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease. Proc Natl Acad Sci USA. 2009;106:5795–800.
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23:549–55.
Covarrubias AJ, Aksoylar HI, Yu J, Snyder NW, Worth AJ, Iyer SS, et al. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. ELife. 2016;5:e11612.
Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, et al. SHIP represses the generation of alternatively activated macrophages. Immunity. 2005;23:361–74.
Sahin-Heco E, Haubenwallner S, Kuttke M, Kollmann I, Halfmann A, Dohnal A, et al. Macrophage PTEN regulates expression and secretion of arginase I modulating innate and adaptive immune responses. J Immunol. 2014;193:1717–27.
Yue S, Rao J, Zhu J, Busuttil R, Kupiec-Weglinski J, Lu L, et al. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation. J Immunol. 2014;192:5343–53.
Linton MF, Moslehi JJ, Babaev VR. Akt signaling in macrophage polarization, survival, and atherosclerosis. Int J Mol Sci. 2019;20:2703.
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253–68.
Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, et al. PI3Kgamma is a molecular switch that controls immune suppression. Nature. 2016;539:437–42.
Aksoy E, Vanden Berghe W, Detienne S, Amraoui Z, Fitzgerald KA, Haegeman G, et al. Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-κB activation and IFN-β synthesis downstream of Toll-like receptor 3 and 4. Eur J Immunol. 2005;35:2200–9.
Fukao T, Tanabe M, Terauchi Y, Ota T, Matsuda S, Asano T, et al. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol. 2002;3:875–81.
Guha M, Mackman N. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem. 2002;277:32124–32.
Wynn TA. Myeloid-cell differentiation redefined in cancer. Nat Immunol. 2013;14:197–9.
Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 2016;37:208–20.
Gyori D, Chessa T, Hawkins PT, Stephens LR. Class (I) phosphoinositide 3-kinases in the tumor microenvironment. Cancers. 2017;9:24.
Soler A, Angulo-Urarte A, Graupera M. PI3K at the crossroads of tumor angiogenesis signaling pathways. Mol Cell Oncol. 2015;2:e975624.
Castel P, Carmona FJ, Grego-Bessa J, Berger MF, Viale A, Anderson KV, et al. Somatic PIK3CA mutations as a driver of sporadic venous malformations. Sci Transl Med. 2016;8:332ra42.
Liu T, Han C, Wang S, Fang P, Ma Z, Xu L, et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J Hematol Oncol. 2019;12:86.
Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, et al. Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature. 2009;461:1084–91.
Jablonska-Trypuc A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzym Inhib Med Chem. 2016;31:177–83.
Awad AE, Kandalam V, Chakrabarti S, Wang X, Penninger JM, Davidge ST, et al. Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner. Am J Physiol Cell Physiol. 2010;298:C679–92.
Li Z, Zhou J, Zhang J, Li S, Wang H, Du J. Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. Int J Cancer. 2019;145:1946–57.
Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6:202–16.
Dong Y, Richards JA, Gupta R, Aung P, Emley A, Kluger Y, et al. PTEN functions as a melanoma tumor suppressor by promoting host immune response. Oncogene. 2013;33:4632–42.
Wada J, Suzuki H, Fuchino R, Yamasaki A, Nagai S, Yanai K, et al. The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions. Anticancer Res. 2009;29:881–8.
Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, et al. Expression of vascular endothelial growth factor in ovarian cancer inhibits tumor immunity through the accumulation of myeloid-derived suppressor cells. Clin Cancer Res. 2017;23:587.
Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13:140–56.
Stamatkin C, Ratermann KL, Overley CW, Black EP. Inhibition of class IA PI3K enzymes in non-small cell lung cancer cells uncovers functional compensation among isoforms. Cancer Biol Ther. 2015;16:1341–52.
Borcoman E, De La Rochère P, Richer W, Vacher S, Chemlali W, Krucker C, et al. Inhibition of PI3K pathway increases immune infiltrate in muscle-invasive bladder cancer. Oncoimmunology. 2019;8:1–17.
Sai J, Owens P, Novitskiy S, Hawkins O, Vilgelm A, Yang J, et al. PI3K inhibition reduces mammary tumor growth and facilitates antitumor immunity and anti-PD1 responses. Clin Cancer Res. 2017;23:3371–84.
Joshi S, Singh AR, Zulcic M, Durden DL. A macrophage-dominant PI3K isoform controls hypoxia-induced HIF1α and HIF2α stability and tumor growth, angiogenesis, and metastasis. Mol Cancer Res. 2014;12:1520.
Abu Eid R, Samara RN, Ozbun L, Abdalla MY, Berzofsky JA, Friedman KM, et al. Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway. Cancer Immunol Res. 2014;2:1080–9.
Zheng W, O’Hear CE, Alli R, Basham JH, Abdelsamed HA, Palmer LE, et al. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia. 2018;32:1157–67.
Marshall N, Galvin K, Corcoran AM, Boon L, Higgs R, Mills K. Immunotherapy with PI3K inhibitor and toll-like receptor agonist induces IFN-gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Res. 2011;72:581–91.
Wang X, Ding J, Meng LH. PI3K isoform-selective inhibitors: next-generation targeted cancer therapies. Acta Pharmacol Sin. 2015;36:1170–6.
Soler A, Figueiredo AM, Castel P, Martin L, Monelli E, Angulo-Urarte A, et al. Therapeutic benefit of selective inhibition of p110α PI3-kinase in pancreatic neuroendocrine tumors. Clin Cancer Res. 2016;22:5805.
Shi JJ, Xing H, Wang YX, Zhang X, Zhan QM, Geng MY, et al. PI3Kalpha inhibitors sensitize esophageal squamous cell carcinoma to radiation by abrogating survival signals in tumor cells and tumor microenvironment. Cancer Lett. 2019;459:145–55.
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, et al. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. J Clin Invest. 2019;129:3264–76.
Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol. 2019;16:601–20.
Pan Y, Jia LP, Liu Y, Han Y, Deng Q. Alteration of tumor associated neutrophils by PIK3CA expression in endometrial carcinoma from TCGA data. J Ovarian Res. 2019;12:81.
Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, et al. Essential roles of PI3K-p110beta in cell growth, metabolism and tumorigenesis. Nature. 2008;454:776–9.
Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci USA. 2008;105:7797–802.
Rausch M, Tchaicha J, Tibbitts T, Henau OD, Sharma S, Pink M, et al. Abstract B032: The PI3K-γ inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment. Cancer Immunol Res. 2016;4:B032.
De Henau O, Rausch M, Winkler D, Campesato LF, Liu C, Cymerman DH, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature. 2016;539:443–7.
Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, et al. Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression. Cancer Discov. 2016;6:870–85.
Peluso M, Faia K, Winkler D, Patel N, Brophy E, White K, et al. Duvelisib (IPI-145) inhibits malignant b-cell proliferation and disrupts signaling from the tumor microenvironment through mechanisms that are dependent on PI3K-δ and PI3K-γ. Blood. 2014;124:328.
Abu-Eid R, Samara RN, Ozbun L, Abdalla MY, Berzofsky JA, Friedman KM, et al. Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway. Cancer Immunol Res. 2014;2:1080–9.
Chellappa S, Kushekhar K, Munthe LA, Tjønnfjord GE, Aandahl EM, Okkenhaug K, et al. The PI3K p110δ isoform inhibitor idelalisib preferentially inhibits human regulatory T cell function. J Immunol. 2019;202:1397–405.
Abu Eid R, Ahmad S, Lin Y, Webb M, Berrong Z, Shrimali R, et al. Enhanced therapeutic efficacy and memory of tumor-specific CD8 T cells by ex vivo PI3K-delta inhibition. Cancer Res. 2017;77:4135–45.
Bowers J, Majchrzak K, Nelson M, Aksoy B, Wyatt M, Smith A, et al. PI3Kδ inhibition enhances the antitumor fitness of adoptively transferred CD8+ T cells. Front Immunol. 2017;8:1221.
O’Donnell JS, Massi D, Teng MWL, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol. 2018;48:91–103.
Zhang H, Chen J. Current status and future directions of cancer immunotherapy. J Cancer. 2018;9:1773–81.
Sambi M, Bagheri L, Szewczuk M. Current challenges in cancer immunotherapy: multimodal approaches to improve efficacy and patient response rates. J Oncol. 2019;2019:1–12.
Alatrash G, Jakher H, Stafford PD, Mittendorf EA. Cancer immunotherapies, their safety and toxicity. Expert Opin Drug Saf. 2013;12:631–45.
Tawbi HAH, Peng W, Milton D, Amaria RN, Glitza IC, Hwu WJ, et al. Phase I/II study of the PI3Kβ inhibitor GSK2636771 in combination with pembrolizumab (P) in patients (pts) with PD-1 refractory metastatic melanoma (MM) and PTEN loss. J Clin Oncol. 2018;36:TPS9596.
Davis RJ, Moore EC, Clavijo PE, Friedman J, Cash H, Chen Z, et al. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kdelta/gamma. Cancer Res. 2017;77:2607–19.
Sullivan RJ, Hong DS, Tolcher AW, Patnaik A, Shapiro G, Chmielowski B, et al. Initial results from first-in-human study of IPI-549, a tumor macrophage-targeting agent, combined with nivolumab in advanced solid tumors. J Clin Oncol. 2018;36:3013.
Weir GM, Liwski RS, Mansour M. Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. Cancers. 2011;3:3114–42.
Kobayashi Y, Lim SO, Yamaguchi H. Oncogenic signaling pathways associated with immune evasion and resistance to immune checkpoint inhibitors in cancer. In: Seminars in cancer biology. Academic Press; 2019.
Choi JH, Kim KH, Roh KH, Jung H, Lee A, Lee JY, et al. A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice. Oncoimmunology. 2018;7:e1421890.
This work was supported by “Personalized Medicines-Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020111, XDA12020235, and XDA12050407]; National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program” [2018ZX09711002-011-014 and 2018ZX09711002-004-004] and National Natural Science Foundation of China [81773760 and 81973345]. It was also partially supported by the Fudan-SIMM Joint Research Fund [FU-SIMM20172005].
The authors declare no competing interests.
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Sun, P., Meng, Lh. Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity. Acta Pharmacol Sin 41, 1395–1402 (2020). https://doi.org/10.1038/s41401-020-00500-8
- phosphoinositide 3-kinase (PI3K)
- PI3K inhibitors
- tumor microenvironment
- immune cells
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