Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases

English version

Autoři: Shotaro Sakimura ^aff001; Satoshi Nagayama ^aff003; Mitsuko Fukunaga ^aff001; Qingjiang Hu ^aff001; Akihiro Kitagawa ^aff001; Yuta Kobayashi ^aff001; Takanori Hasegawa ^aff004; Miwa Noda ^aff001; Yuta Kouyama ^aff001; Dai Shimizu ^aff001; Tomoko Saito ^aff001; Atsushi Niida ^aff005; Yusuke Tsuruda ^aff001; Hajime Otsu ^aff001; Yoshihiro Matsumoto ^aff001; Hiroki Uchida ^aff001; Takaaki Masuda ^aff001; Keishi Sugimachi ^aff001; Shin Sasaki ^aff006; Kazutaka Yamada ^aff007; Kazuki Takahashi ^aff008; Hideki Innan ^aff008; Yutaka Suzuki ^aff009; Hiromi Nakamura ^aff010; Yasushi Totoki ^aff010; Shinichi Mizuno ^aff011; Masanobu Ohshima ^aff012; Tatsuhiro Shibata ^aff010; Koshi Mimori ^aff001
Působiště autorů: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan ^aff001; Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ^aff002; Gastroenterological Center, Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan ^aff003; Division of Health Medical Data Science, Health Intelligence Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan ^aff004; Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan ^aff005; Department of Surgery, Omori Red Cross Hospital, Tokyo, Japan ^aff006; Department of Surgery, Takano Hospital, Kumamoto, Japan ^aff007; Department of Evolutionary Studies of Biosystems, SOKENDAI, The Graduate University for Advanced Studies, Tokyo, Japan ^aff008; Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan ^aff009; Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan ^aff010; Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan ^aff011; Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan ^aff012; Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan ^aff013
Vyšlo v časopise: Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases. PLoS Genet 17(1): e1009113. doi:10.1371/journal.pgen.1009113
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009113

Souhrn

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.

Klíčová slova:

Colorectal cancer – Metastasis – Cancer genomics – Evolutionary immunology – Immune response – Metastatic tumors – T cell receptors – T cells

Zdroje

1. Almendro V, Cheng YK, Randles A, Itzkovitz S, Marusyk A, Ametller E, et al. Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity. Cell Reports. 2014;6(3):514–27. doi: 10.1016/j.celrep.2013.12.041 24462293.

2. Gerlinger M, Horswell S, Larkin J, Rowan AJ, Salm MP, Varela I, et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nature Genetics. 2014;46(3):225–33. doi: 10.1038/ng.2891 24487277.

3. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. The New England Journal of Medicine. 2012;366(10):883–92. doi: 10.1056/NEJMoa1113205 22397650.

4. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science. 2014;343(6167):189–93. doi: 10.1126/science.1239947 24336570.

5. Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467(7319):1114–7. doi: 10.1038/nature09515 20981102; PubMed Central PMCID: PMC3148940.

6. Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H, Takeuchi Y, et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 2019;565(7739):312–7. doi: 10.1038/s41586-018-0811-x 30602793.

7. Sottoriva A, Kang H, Ma Z, Graham TA, Salomon MP, Zhao J, et al. A Big Bang model of human colorectal tumor growth. Nature Genetics. 2015;47(3):209–16. doi: 10.1038/ng.3214 25665006; PubMed Central PMCID: PMC4575589.

8. Uchi R, Takahashi Y, Niida A, Shimamura T, Hirata H, Sugimachi K, et al. Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. PLoS Genetics. 2016;12(2):e1005778. doi: 10.1371/journal.pgen.1005778 26890883; PubMed Central PMCID: PMC4758664.

9. Saito T, Niida A, Uchi R, Hirata H, Komatsu H, Sakimura S, et al. A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer. Nature Communications. 2018;9(1):2884. doi: 10.1038/s41467-018-05226-0 30038269; PubMed Central PMCID: PMC6056524.

10. Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al. Tracking the Evolution of Non-Small-Cell Lung Cancer. The New England Journal of Medicine. 2017;376(22):2109–21. doi: 10.1056/NEJMoa1616288 28445112.

11. Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018;553(7689):467–72. doi: 10.1038/nature25432 29342134; PubMed Central PMCID: PMC5785464.

12. Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017;355(6322). doi: 10.1126/science.aaf8399 28104840.

13. Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, et al. Genomic and Functional Approaches to Understanding Cancer Aneuploidy. Cancer Cell. 2018;33(4):676–89 e3. doi: 10.1016/j.ccell.2018.03.007 29622463.

14. Hemon P, Jean-Louis F, Ramgolam K, Brignone C, Viguier M, Bachelez H, et al. MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. Journal of immunology. 2011;186(9):5173–83. doi: 10.4049/jimmunol.1002050 21441454.

15. Fang H, Yamaguchi R, Liu X, Daigo Y, Yew PY, Tanikawa C, et al. Quantitative T cell repertoire analysis by deep cDNA sequencing of T cell receptor alpha and beta chains using next-generation sequencing (NGS). Oncoimmunology. 2014;3(12):e968467. Epub 2015/05/13. doi: 10.4161/21624011.2014.968467 25964866; PubMed Central PMCID: PMC4368121.

16. Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nature Medicine. 2015;21(11):1350–6. doi: 10.1038/nm.3967 26457759; PubMed Central PMCID: PMC4636487.

17. Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018;362(6411). doi: 10.1126/science.aar3593 30309915.

18. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. The EMBO journal. 1992;11(11):3887–95. 1396582; PubMed Central PMCID: PMC556898.

19. McGranahan N, Rosenthal R, Hiley CT, Rowan AJ, Watkins TBK, Wilson GA, et al. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell. 2017;171(6):1259–71 e11. doi: 10.1016/j.cell.2017.10.001 29107330; PubMed Central PMCID: PMC5720478.

20. Bhati M, Cole DK, McCluskey J, Sewell AK, Rossjohn J. The versatility of the alphabeta T-cell antigen receptor. Protein science: a publication of the Protein Society. 2014;23(3):260–72. doi: 10.1002/pro.2412 24375592; PubMed Central PMCID: PMC3945834.

21. Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nature Genetics. 2013;45(10):1113–20. doi: 10.1038/ng.2764 24071849; PubMed Central PMCID: PMC3919969.

22. Mamedov IZ, Britanova OV, Zvyagin IV, Turchaninova MA, Bolotin DA, Putintseva EV, et al. Preparing unbiased T-cell receptor and antibody cDNA libraries for the deep next generation sequencing profiling. Frontiers in Immunology. 2013;4 : 456. doi: 10.3389/fimmu.2013.00456 24391640; PubMed Central PMCID: PMC3870325.

23. Shugay M, Britanova OV, Merzlyak EM, Turchaninova MA, Mamedov IZ, Tuganbaev TR, et al. Towards error-free profiling of immune repertoires. Nature Methods. 2014;11(6):653–5. doi: 10.1038/nmeth.2960 24793455.

24. Shugay M, Bagaev DV, Turchaninova MA, Bolotin DA, Britanova OV, Putintseva EV, et al. VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires. PLoS Computational Biology. 2015;11(11):e1004503. doi: 10.1371/journal.pcbi.1004503 26606115; PubMed Central PMCID: PMC4659587.

25. Van Loo P, Nordgard SH, Lingjaerde OC, Russnes HG, Rye IH, Sun W, et al. Allele-specific copy number analysis of tumors. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(39):16910–5. doi: 10.1073/pnas.1009843107 20837533; PubMed Central PMCID: PMC2947907.

26. Magi A, Tattini L, Cifola I, D'Aurizio R, Benelli M, Mangano E, et al. EXCAVATOR: detecting copy number variants from whole-exome sequencing data. Genome Biology. 2013;14(10):R120. doi: 10.1186/gb-2013-14-10-r120 24172663; PubMed Central PMCID: PMC4053953.

27. Romero JM, Grunwald BT, Jang GH, Bavi PP, Jhaveri A, Masoomian M, et al. A four-chemokine signature is associated with a T cell-inflamed phenotype in primary and metastatic pancreatic cancer. Clinical Cancer Research Epub 2020/01/23. doi: 10.1158/1078-0432.CCR-19-2803 31964786.

28. Shiraishi Y, Sato Y, Chiba K, Okuno Y, Nagata Y, Yoshida K, et al. An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data. Nucleic Acids Research. 2013;41(7):e89. doi: 10.1093/nar/gkt126 23471004; PubMed Central PMCID: PMC3627598.

Článek MED19 alters AR occupancy and gene expression in prostate cancer cells, driving MAOA expression and growth under low androgen

Článek Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans

Článek The clarifying role of time series data in the population genetics of HIV

Článek Population structure of indigenous inhabitants of Arabia

Článek Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome

Článek Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect

Článek Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Článek A rare coding mutation in the MAST2 gene causes venous thrombosis in a French family with unexplained thrombophilia: The Breizh MAST2 Arg89Gln variant

Článek Genome-scale CRISPR screening for modifiers of cellular LDL uptake

Článek Htt is a repressor of Abl activity required for APP-induced axonal growth

Článek Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling

Článek Epithelial cell-turnover ensures robust coordination of tissue growth in Drosophila ribosomal protein mutants