Cancer stem cells and niches: challenges in immunotherapy resistance

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):64548.

Article CAS PubMed Google Scholar

Saw PE, Liu Q, Wong PP, Song E. Cancer stem cell mimicry for immune evasion and therapeutic resistance. Cell Stem Cell. 2024;31(8):110112.

Article CAS PubMed Google Scholar

Beerling E, Seinstra D, de Wit E, Kester L, van der Velden D, Maynard C, Schfer R, van Diest P, Voest E, van Oudenaarden A, et al. Plasticity between epithelial and mesenchymal States unlinks EMT from metastasis-enhancing stem cell capacity. Cell Rep. 2016;14(10):228188.

Article CAS PubMed PubMed Central Google Scholar

Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Gktuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 2013;152(12):2538.

Article CAS PubMed Google Scholar

Schaub JR, Huppert KA, Kurial S, Hsu BY, Cast AE, Donnelly B, Karns RA, Chen F, Rezvani M, Luu HY, et al. De novo formation of the biliary system by TGF-mediated hepatocyte transdifferentiation. Nature. 2018;557(7704):24751.

Article CAS PubMed PubMed Central Google Scholar

Saha S, Mukherjee S, Khan P, Kajal K, Mazumdar M, Manna A, Mukherjee S, De S, Jana D, Sarkar DK, et al. Aspirin suppresses the Acquisition of Chemoresistance in breast Cancer by disrupting an NFB-IL6 signaling Axis responsible for the generation of Cancer Stem cells. Cancer Res. 2016;76(7):200012.

Article CAS PubMed Google Scholar

Francescangeli F, Contavalli P, De Angelis ML, Careccia S, Signore M, Haas TL, Salaris F, Baiocchi M, Boe A, Giuliani A, et al. A pre-existing population of ZEB2(+) quiescent cells with stemness and mesenchymal features dictate chemoresistance in colorectal cancer. J Exp Clin Cancer Res. 2020;39(1):2.

Article CAS PubMed PubMed Central Google Scholar

Beziaud L, Young CM, Alonso AM, Norkin M, Minafra AR, Huelsken J. IFN-induced stem-like state of cancer cells as a driver of metastatic progression following immunotherapy. Cell Stem Cell. 2023;30(6):818e316.

Article CAS PubMed Google Scholar

Oliveira G, Wu CJ. Dynamics and specificities of T cells in cancer immunotherapy. Nat Rev Cancer. 2023;23(5):295316.

Article CAS PubMed PubMed Central Google Scholar

ODonnell JS, Teng M, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):15167.

Article PubMed Google Scholar

Saygin C, Matei D, Majeti R, Reizes O, Lathia JD. Targeting Cancer Stemness in the clinic: from hype to Hope. Cell Stem Cell. 2019;24(1):2540.

Article CAS PubMed Google Scholar

Liau BB, Sievers C, Donohue LK, Gillespie SM, Flavahan WA, Miller TE, Venteicher AS, Hebert CH, Carey CD, Rodig SJ, et al. Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance. Cell Stem Cell. 2017;20(2):233.46.e7.

Article CAS PubMed Google Scholar

Rambow F, Rogiers A, Marin-Bejar O, Aibar S, Femel J, Dewaele M, Karras P, Brown D, Chang YH, Debiec-Rychter M, et al. Toward minimal residual Disease-Directed Therapy in Melanoma. Cell. 2018;174(4):843e5519.

Article CAS PubMed Google Scholar

Lemaitre L, Adeniji N, Suresh A, Reguram R, Zhang J, Park J, Reddy A, Trevino AE, Mayer AT, Deutzmann A, et al. Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease. Nat Cancer. 2024;5(10):153456.

Article CAS PubMed Google Scholar

Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol. 2019;20(5):30320.

Article CAS PubMed PubMed Central Google Scholar

Hirakawa H, Gao L, Tavakol DN, Vunjak-Novakovic G, Ding L. Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration. Nat Genet. 2023;55(11):194152.

Article CAS PubMed Google Scholar

Hurwitz SN, Jung SK, Kurre P. Hematopoietic stem and progenitor cell signaling in the niche. Leukemia. 2020;34(12):313648.

Article PubMed Google Scholar

Kann AP, Hung M, Krauss RS. Cell-cell contact and signaling in the muscle stem cell niche. Curr Opin Cell Biol. 2021;73:7883.

Article CAS PubMed PubMed Central Google Scholar

Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells. Cell Stem Cell. 2015;16(3):22538.

Article CAS PubMed PubMed Central Google Scholar

Raggi C, Correnti M, Sica A, Andersen JB, Cardinale V, Alvaro D, Chiorino G, Forti E, Glaser S, Alpini G, et al. Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages. J Hepatol. 2017;66(1):10215.

Article CAS PubMed Google Scholar

Hide T, Komohara Y, Miyasato Y, Nakamura H, Makino K, Takeya M, Kuratsu JI, Mukasa A, Yano S. Oligodendrocyte progenitor cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border. EBioMedicine. 2018;30:94104.

Article CAS PubMed PubMed Central Google Scholar

Lu H, Clauser KR, Tam WL, Frse J, Ye X, Eaton EN, Reinhardt F, Donnenberg VS, Bhargava R, Carr SA, et al. A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages. Nat Cell Biol. 2014;16(11):110517.

Article CAS PubMed PubMed Central Google Scholar

Zhang H, Wang Y, Yuan X, Zou Y, Xiong H. Research progress on lung cancer stem cells in epidermal growth factor receptortyrosine kinase inhibitor targeted therapy resistance in lung adenocarcinoma. Oncol Translational Med. 2024;10(1).

Wei JR, Zhang B, Zhang Y, Chen WM, Zhang XP, Zeng TT, Li Y, Zhu YH, Guan XY, Li L. QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion. Proc Natl Acad Sci U S A. 2024;121(44):e2407506121.

Article CAS PubMed Google Scholar

Goto N, Westcott P, Goto S, Imada S, Taylor MS, Eng G, Braverman J, Deshpande V, Jacks T, Agudo J, et al. SOX17 enables immune evasion of early colorectal adenomas and cancers. Nature. 2024;627(8004):63645.

Article CAS PubMed Google Scholar

Su W, Han HH, Wang Y, Zhang B, Zhou B, Cheng Y, Rumandla A, Gurrapu S, Chakraborty G, Su J, et al. The polycomb Repressor Complex 1 drives double-negative prostate Cancer Metastasis by coordinating stemness and Immune suppression. Cancer Cell. 2019;36(2):139e5510.

Article CAS PubMed PubMed Central Google Scholar

Chulpanova DS, Rizvanov AA, Solovyeva VV. The role of Cancer Stem cells and their extracellular vesicles in the modulation of the Antitumor immunity. Int J Mol Sci. 2022;24(1):395.

Article PubMed PubMed Central Google Scholar

Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer. 2022;21(1):28.

Article PubMed PubMed Central Google Scholar

Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, Gouw AM, Baylot V, Gtgemann I, Eilers M, et al. MYC regulates the antitumor immune response through CD47 and PD-L1. Science. 2016;352(6282):22731.

Article CAS PubMed PubMed Central Google Scholar

Fu L, Fan J, Maity S, McFadden G, Shi Y, Kong W. PD-L1 interacts with frizzled 6 to activate -catenin and form a positive feedback loop to promote cancer stem cell expansion. Oncogene. 2022;41(8):110013.

Article CAS PubMed Google Scholar

Lpez Flores M, Honrado Franco E, Snchez Cousido LF, Minguito-Carazo C, Sanz Guadarrama O, Lpez Gonzlez L, Vallejo Pascual ME, Molina de la Torre AJ, Garca Palomo A, Lpez Gonzlez A. Relationship between Aldehyde dehydrogenase, PD-L1 and tumor-infiltrating lymphocytes with pathologic response and survival in breast Cancer. Cancers (Basel). 2022;14(18):4418.

Article PubMed Google Scholar

Mansour FA, Al-Mazrou A, Al-Mohanna F, Al-Alwan M, Ghebeh H. PD-L1 is overexpressed on breast cancer stem cells through notch3/mTOR axis. Oncoimmunology. 2020;9(1):1729299.

Article PubMed PubMed Central Google Scholar

Wu Y, Chen M, Wu P, Chen C, Xu ZP, Gu W. Increased PD-L1 expression in breast and colon cancer stem cells. Clin Exp Pharmacol Physiol. 2017;44(5):60204.

Article CAS PubMed Google Scholar

Hsu JM, Xia W, Hsu YH, Chan LC, Yu WH, Cha JH, Chen CT, Liao HW, Kuo CW, Khoo KH, et al. STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nat Commun. 2018;9(1):1908.

Article PubMed PubMed Central Google Scholar

Zhi Y, Mou Z, Chen J, He Y, Dong H, Fu X, Wu Y. B7H1 expression and Epithelial-To-Mesenchymal transition phenotypes on Colorectal Cancer Stem-Like cells. PLoS ONE. 2015;10(8):e0135528.

Article PubMed PubMed Central Google Scholar

Lee Y, Shin JH, Longmire M, Wang H, Kohrt HE, Chang HY, Sunwoo JB. CD44+cells in Head and Neck squamous cell Carcinoma suppress T-Cell-mediated immunity by selective constitutive and inducible expression of PD-L1. Clin Cancer Res. 2016;22(14):357181.

Article CAS PubMed PubMed Central Google Scholar

Yao Y, Ye H, Qi Z, Mo L, Yue Q, Baral A, Hoon D, Vera JC, Heiss JD, Chen CC, et al. B7-H4(B7x)-Mediated cross-talk between glioma-initiating cells and macrophages via the IL6/JAK/STAT3 pathway lead to poor prognosis in Glioma patients. Clin Cancer Res. 2016;22(11):277890.

Article CAS PubMed PubMed Central Google Scholar

Liu Y, John P, Nishitani K, Cui J, Nishimura CD, Christin JR, Couturier N, Ren X, Wei Y, Pulanco MC, et al. A SOX9-B7x axis safeguards dedifferentiated tumor cells from immune surveillance to drive breast cancer progression. Dev Cell. 2023;58(23):2700e1712.

Article CAS PubMed PubMed Central Google Scholar

Wang C, Li Y, Jia L, Kim JK, Li J, Deng P, Zhang W, Krebsbach PH, Wang CY. CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance. Cell Stem Cell. 2021;28(9):1597e6137.

Article CAS PubMed PubMed Central Google Scholar

Miao Y, Yang H, Levorse J, Yuan S, Polak L, Sribour M, Singh B, Rosenblum MD, Fuchs E. Adaptive Immune Resistance emerges from Tumor-initiating stem cells. Cell. 2019;177(5):1172e8614.

Article CAS PubMed PubMed Central Google Scholar

Yang C, Geng H, Yang X, Ji S, Liu Z, Feng H, et al. Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy. Cancer Cell. 2024;42(12):206481.e19.

Zhou R, Chen S, Wu Q, Liu L, Wang Y, Mo Y, Zeng Z, Zu X, Xiong W, Wang F. CD155 and its receptors in cancer immune escape and immunotherapy. Cancer Lett. 2023;573:216381.

Article CAS PubMed Google Scholar

Barkal AA, Brewer RE, Markovic M, Kowarsky M, Barkal SA, Zaro BW, Krishnan V, Hatakeyama J, Dorigo O, Barkal LJ, et al. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019;572(7769):39296.

Article CAS PubMed PubMed Central Google Scholar

Altevogt P, Sammar M, Hser L, Kristiansen G. Novel insights into the function of CD24: a driving force in cancer. Int J Cancer. 2021;148(3):54659.

Article CAS PubMed Google Scholar

Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):28699.

Article CAS PubMed PubMed Central Google Scholar

Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R, Traver D, van Rooijen N, Weissman IL. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009;138(2):27185.

Article CAS PubMed PubMed Central Google Scholar

Su Z, Dong S, Chen Y, Huang T, Qin B, Yang Q, Jiang X, Zou C. Microfluidics-enabled nanovesicle delivers CD47/PD-L1 antibodies to Enhance Antitumor Immunity and reduce immunotoxicity in Lung Adenocarcinoma. Adv Sci (Weinh). 2023;10(20):e2206213.

Article PubMed Google Scholar

Pan Y, Lu F, Fei Q, Yu X, Xiong P, Yu X, Dang Y, Hou Z, Lin W, Lin X, et al. Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer. J Hematol Oncol. 2019;12(1):124.

Article CAS PubMed PubMed Central Google Scholar

Wang J, Lu Q, Chen X, Aifantis I. Targeting MHC-I inhibitory pathways for cancer immunotherapy. Trends Immunol. 2024;45(3):17787.

Article CAS PubMed Google Scholar

Wu X, Li T, Jiang R, Yang X, Guo H, Yang R. Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects. Mol Cancer. 2023;22(1):194.

Article CAS PubMed PubMed Central Google Scholar

Yang K, Halima A, Chan TA. Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy. Nat Rev Clin Oncol. 2023;20(9):60423.

Article CAS PubMed Google Scholar

Read this article:

Cancer stem cells and niches: challenges in immunotherapy resistance