Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade

References

• St Paul M, Ohashi PS. The Roles of CD8(+) T Cell Subsets in Antitumor Immunity. Trends Cell Biol. 2020;30:695–16. doi:10.1016/j.tcb.2020.06.003.
   PubMed Web of Science ®Google Scholar
• Tay RE, Richardson EK, Toh HC. Revisiting the role of CD4(+) T cells in cancer immunotherapy-new insights into old paradigms. Cancer Gene Ther. 2021;28:5–17. doi:10.1038/s41417-020-0183-x.
   PubMed Web of Science ®Google Scholar
• Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20:651–668.
   PubMed Web of Science ®Google Scholar
• Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020;11:3801. doi:10.1038/s41467-020-17670-y.
   PubMed Web of Science ®Google Scholar
• Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168:707–723. doi:10.1016/j.cell.2017.01.017.
   PubMed Web of Science ®Google Scholar
• Jensen BA, Pedersen SR, Christensen JP, Thomsen AR, Bachmann MP. The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies. PLoS One. 2013;8:e66081. doi:10.1371/journal.pone.0066081.
   PubMed Web of Science ®Google Scholar
• Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell. 2021;39:154–173. doi:10.1016/j.ccell.2020.10.001.
   PubMed Web of Science ®Google Scholar
• Anagnostou V, Bruhm, D. C., Niknafs, N., White, J. R., Shao, X. M., Sidhom, J. W. & Velculescu, V. E. Integrative tumor and immune cell multi-omic analyses predict response to immune checkpoint blockade in Melanoma. Cell Rep Med. 2020;1:100139. doi:10.1016/j.xcrm.2020.100139.
   PubMedGoogle Scholar
• Lee M, Samstein RM, Valero C, Chan TA, Morris LGT. Tumor mutational burden as a predictive biomarker for checkpoint inhibitor immunotherapy. Hum Vaccin Immunother. 2020;16:112–115. doi:10.1080/21645515.2019.1631136.
   PubMed Web of Science ®Google Scholar
• Maleki Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer. 2018;6:157. doi:10.1186/s40425-018-0479-7.
   PubMed Web of Science ®Google Scholar
• Litchfield K, Reading JL, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins TBK, Rosenthal R, Biswas D, Rowan A, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell. 2021;184:596–614 e514. doi:10.1016/j.cell.2021.01.002.
   PubMed Web of Science ®Google Scholar
• Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–206. doi:10.1038/s41588-018-0312-8.
   PubMed Web of Science ®Google Scholar
• Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer. 2008;8:24–36. doi:10.1038/nrc2292.
   PubMed Web of Science ®Google Scholar
• Nielsen SN, Grell K, Nersting J, Abrahamsson J, Lund B, Kanerva J, Jónsson ÓG, Vaitkeviciene G, Pruunsild K, Hjalgrim LL, et al. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. Lancet Oncol. 2017;18:515–524. doi:10.1016/S1470-2045(17)30154-7.
   PubMed Web of Science ®Google Scholar
• Toksvang LN, Als-Nielsen B, Bacon C, Bertasiute R, Duarte X, Escherich G, Helgadottir EA, Johannsdottir IR, Jónsson ÓG, Kozlowski P, et al. Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol. BMC Cancer. 2022;22:483. doi:10.1186/s12885-022-09522-3.
   PubMed Web of Science ®Google Scholar
• Larsen RH, Utke Rank C, Grell K, Nørgaard Møller L, Malthe Overgaard U, Kampmann P, Nersting J, Degn M, Nygaard Nielsen S, Holst H, et al. Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia. Haematologica. 2021;106:2824–2833. doi:10.3324/haematol.2020.278166.
   PubMed Web of Science ®Google Scholar
• Meeth K, Wang JX, Micevic G, Damsky W, Bosenberg MW. The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations. Pigment Cell Melanoma Res. 2016;29:590–597. doi:10.1111/pcmr.12498.
   PubMed Web of Science ®Google Scholar
• Homet Moreno B, Zaretsky JM, Garcia-Diaz A, Tsoi J, Parisi G, Robert L, Meeth K, Ndoye A, Bosenberg M, Weeraratna AT, et al. Response to programmed cell death-1 blockade in a murine Melanoma syngeneic model requires costimulation, CD4, and CD8 T cells. Cancer Immunol Res. 2016;4:845–857. doi:10.1158/2326-6066.CIR-16-0060.
   PubMed Web of Science ®Google Scholar
• Di Leo L, Bodemeyer V, Bosisio FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, et al. Loss of Ambra1 promotes melanoma growth and invasion. Nat Commun. 2021;12:2550. doi:10.1038/s41467-021-22772-2.
   PubMed Web of Science ®Google Scholar
• Jacobsen JH, Schmiegelow K, Nersting J. Liquid chromatography-tandem mass spectrometry quantification of 6-thioguanine in DNA using endogenous guanine as internal standard. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;881-882:115–118. doi:10.1016/j.jchromb.2011.11.032.
   PubMed Web of Science ®Google Scholar
• Shipkova M, Armstrong VW, Wieland E, Oellerich M. Differences in nucleotide hydrolysis contribute to the differences between erythrocyte 6-thioguanine nucleotide concentrations determined by two widely used methods. Clin Chem. 2003;49:260–268. doi:10.1373/49.2.260.
   PubMed Web of Science ®Google Scholar
• Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010;26:589–595. doi:10.1093/bioinformatics/btp698.
   PubMed Web of Science ®Google Scholar
• McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, et al. The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–1303. doi:10.1101/gr.107524.110.
   PubMed Web of Science ®Google Scholar
• Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, Gabriel S, Meyerson M, Lander ES, Getz G, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31:213–219. doi:10.1038/nbt.2514.
   PubMed Web of Science ®Google Scholar
• Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164. doi:10.1093/nar/gkq603.
   PubMed Web of Science ®Google Scholar
• Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018;28:1747–1756. doi:10.1101/gr.239244.118.
   PubMed Web of Science ®Google Scholar
• Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21. doi:10.1093/bioinformatics/bts635.
   PubMed Web of Science ®Google Scholar
• Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi:10.1186/s13059-014-0550-8.
   PubMed Web of Science ®Google Scholar
• Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–15550. doi:10.1073/pnas.0506580102.
   PubMed Web of Science ®Google Scholar
• Monteiro LB, Davanzo GG, de Aguiar CF, Moraes-Vieira PMM. Using flow cytometry for mitochondrial assays. MethodsX. 2020;7:100938. doi:10.1016/j.mex.2020.100938.
   PubMed Web of Science ®Google Scholar
• Toksvang LN, Grell K, Nielsen SN, Nersting J, Murdy D, Moorman AV, Vora A, Schmiegelow K. DNA-TG and risk of sinusoidal obstruction syndrome in childhood acute lymphoblastic leukemia. Leukemia. 2022;36:555–557. doi:10.1038/s41375-021-01420-0.
   PubMed Web of Science ®Google Scholar
• Toksvang LN, Grell K, Nersting J, Degn M, Nielsen SN, Abrahamsson J, Lund B, Kanerva J, Jónsson ÓG, Lepik K, et al. DNA-thioguanine concentration and relapse risk in children and young adults with acute lymphoblastic leukemia: an IPD meta-analysis. Leukemia. 2022;36:33–41. doi:10.1038/s41375-021-01182-9.
   PubMed Web of Science ®Google Scholar
• Fucikova J, Kepp, O., Kasikova, L., Petroni, G., Yamazaki, T., Liu, P., & Galluzzi, L. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 2020;11:1013. doi:10.1038/s41419-020-03221-2.
   PubMed Web of Science ®Google Scholar
• Wang P, Chen Y, Wang C. Beyond tumor mutation burden: tumor neoantigen burden as a biomarker for immunotherapy and other types of therapy. Front Oncol. 2021;11:672677. doi:10.3389/fonc.2021.672677.
   PubMed Web of Science ®Google Scholar
• Fujimura T, Kambayashi Y, Aiba S. Crosstalk between regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) during melanoma growth. Oncoimmunology. 2012;1:1433–1434. doi:10.4161/onci.21176.
   PubMed Web of Science ®Google Scholar
• Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P, et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002;277:21453–21457. doi:10.1074/jbc.C200176200.
   PubMed Web of Science ®Google Scholar
• Baeyens A, Fang V, Chen C, Schwab SR. Exit Strategies: S1P Signaling and T Cell Migration. Trends Immunol. 2015;36:778–787. doi:10.1016/j.it.2015.10.005.
   PubMed Web of Science ®Google Scholar
• Lelliott EJ, Cullinane, C., Martin, C. A., Walker, R., Ramsbottom, K. M., Souza-Fonseca-Guimaraes, F., & Sheppard, K. E. A novel immunogenic mouse model of melanoma for the preclinical assessment of combination targeted and immune-based therapy. Sci Rep. 2019;9:1225.
   PubMed Web of Science ®Google Scholar
• Salas-Benito D, Pérez-Gracia JL, Ponz-Sarvisé M, Rodriguez-Ruiz ME, Martínez-Forero I, Castañón E, López-Picazo JM, Sanmamed MF, Melero I. Paradigms on immunotherapy combinations with chemotherapy. Cancer Discov. 2021;11:1353–1367. doi:10.1158/2159-8290.CD-20-1312.
   PubMed Web of Science ®Google Scholar
• Kat A, Thilly WG, Fang WH, Longley MJ, Li GM, Modrich P. An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc Natl Acad Sci U S A. 1993;90:6424–6428. doi:10.1073/pnas.90.14.6424.
   PubMed Web of Science ®Google Scholar
• Branch P, Aquilina G, Bignami M, Karran P. Defective mismatch binding and a mutator phenotype in cells tolerant to DNA damage. Nature. 1993;362:652–654. doi:10.1038/362652a0.
   PubMed Web of Science ®Google Scholar
• Zheng M. Tumor mutation burden for predicting immune checkpoint blockade response: the more, the better. J Immunother Cancer. 2022;10:e003087. doi:10.1136/jitc-2021-003087.
   PubMed Web of Science ®Google Scholar
• Zou XL, Li X-B, Ke H, Zhang G-Y, Tang Q, Yuan J, Zhou C-J, Zhang J-L, Zhang R, Chen W-Y, et al. Prognostic value of neoantigen load in immune checkpoint inhibitor therapy for cancer. Front Immunol. 2021;12:689076. doi:10.3389/fimmu.2021.689076.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res. 2015;21:687–692. doi:10.1158/1078-0432.CCR-14-1860.
   PubMed Web of Science ®Google Scholar
• Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72. doi:10.1146/annurev-immunol-032712-100008.
   PubMed Web of Science ®Google Scholar
• Chamoto K, Hatae R, Honjo T. Current issues and perspectives in PD-1 blockade cancer immunotherapy. Int J Clin Oncol. 2020;25:790–800. doi:10.1007/s10147-019-01588-7.
   PubMed Web of Science ®Google Scholar
• Lei Q, Wang D, Sun K, Wang L, Zhang Y. Resistance mechanisms of anti-PD1/PDL1 therapy in solid tumors. Front Cell Dev Biol. 2020;8:672. doi:10.3389/fcell.2020.00672.
   PubMed Web of Science ®Google Scholar
• Feng J, Chen S, Li S, Wu B, Lu J, Tan L, Li J, Song Y, Shi G, Shi YG, et al. The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients. Transl Oncol. 2020;13:100865. doi:10.1016/j.tranon.2020.100865.
   PubMed Web of Science ®Google Scholar
• Wang J, Perry CJ, Meeth K, Thakral D, Damsky W, Micevic G, Kaech S, Blenman K, Bosenberg M. UV-induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell Melanoma Res. 2017;30:428–435. doi:10.1111/pcmr.12591.
   PubMed Web of Science ®Google Scholar
• Gorgun FM, Widen SG, Tyler DS, Englander EW. Enhanced antitumor response to immune checkpoint blockade exerted by cisplatin-induced mutagenesis in a murine melanoma model. Front Oncol. 2021;11:701968. doi:10.3389/fonc.2021.701968.
   PubMed Web of Science ®Google Scholar