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Cancer Microenvironment

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05.02.2018 | Original Article

Recovery of Immunoglobulin VJ Recombinations from Pancreatic Cancer Exome Files Strongly Correlates with Reduced Survival

verfasst von: Jacob C. Kinskey, Yaping N. Tu, Wei Lue Tong, John M. Yavorski, George Blanck

Erschienen in: Cancer Microenvironment | Ausgabe 1/2018

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Abstract

We assessed pancreatic cancer, lymphocyte infiltrates with a computational genomics approach. We took advantage of tumor-specimen exome files available from the cancer genome atlas to mine T- and B-cell immune receptor recombinations, using highly efficient, scripted algorithms established in several previous reports. Surprisingly, the results indicated that pancreatic cancer exomes represent one of the highest level yields for immune receptor recombinations, significantly higher than two comparison cancers used in this study, head and neck and bladder cancer. In particular, pancreatic cancer exomes have very large numbers of immunoglobulin light chain recombinations, both with regard to number of samples characterized by recovery of such recombinations and with regard to numbers of recombination reads per sample. These results were consistent with B-cell biomarkers, which emphasized the Th2 nature of the pancreatic lymphocyte infiltrate. The tumor specimen exomes with B-cell immune receptor recombination reads represented a dramatically poor outcome, a result not detected with either the head and neck or bladder cancer datasets. The results presented here support the potential value of immunotherapies designed to engineer a Th2 to Th1 shift in treating certain forms of pancreatic cancer.

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Bucheit AD, Davies MA (2014) Emerging insights into resistance to BRAF inhibitors in melanoma. Biochem Pharmacol 87(3):381–389. https://doi.org/10.1016/j.bcp.2013.11.013 CrossRefPubMed

Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404. https://doi.org/10.1158/2159-8290.CD-12-0095 CrossRefPubMed

Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1. https://doi.org/10.1126/scisignal.2004088 CrossRefPubMedPubMedCentral

Ping Z, Siegal GP, Almeida JS, Schnitt SJ, Shen D (2014) Mining genome sequencing data to identify the genomic features linked to breast cancer histopathology. J Pathol Inform 5(1):3. https://doi.org/10.4103/2153-3539.126147 CrossRefPubMedPubMedCentral

Inman BA, Longo TA, Ramalingam S, Harrison MR (2016) Atezolizumab: a PD-L1 blocking antibody for bladder cancer. Clin Cancer Res 23(8):1886–1890. https://doi.org/10.1158/1078-0432.CCR-16-1417 CrossRefPubMed

Gupta S, Gill D, Poole A, Agarwal N (2017) Systemic immunotherapy for urothelial cancer: current trends and future directions. Cancers 9(2). https://doi.org/10.3390/cancers9020015

Margolin K (2016) The promise of molecularly targeted and immunotherapy for advanced melanoma. Curr Treat Options in Oncol 17(9):48. https://doi.org/10.1007/s11864-016-0421-5 CrossRef

Yun S, Vincelette ND, Green MR, Wahner Hendrickson AE, Abraham I (2016) Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta-analysis of anti-CTLA-4 and anti-PD-1 agents trials. Cancer Med 5(7):1481–1491. https://doi.org/10.1002/cam4.732 CrossRefPubMedPubMedCentral

Poschke I, Faryna M, Bergmann F, Flossdorf M, Lauenstein C, Hermes J, Hinz U, Hank T, Ehrenberg R, Volkmar M, Loewer M, Glimm H, Hackert T, Sprick MR, Höfer T, Trumpp A, Halama N, Hassel JC, Strobel O, Büchler M, Sahin U, Offringa R (2016) Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma. Oncoimmunology 5(12):e1240859. https://doi.org/10.1080/2162402X.2016.1240859 CrossRefPubMedPubMedCentral

10.

Gill TR, Samy MD, Butler SN, Mauro JA, Sexton WJ, Blanck G (2016) Detection of productively rearranged TcR-alpha V-J sequences in TCGA exome files: implications for tumor Immunoscoring and recovery of antitumor T-cells. Cancer Inform 15:23–28. https://doi.org/10.4137/CIN.S35784 CrossRefPubMedPubMedCentral

11.

Tong WL, Tu YN, Samy MD, Sexton WJ, Blanck G (2017) Identification of immunoglobulin V(D)J recombinations in solid tumor specimen exome files: evidence for high level B-cell infiltrates in breast cancer. Hum Vaccin Immunother 13(3):1–6. https://doi.org/10.1080/21645515.2016.1246095 CrossRef

12.

Levy E, Marty R, Garate Calderon V, Woo B, Dow M, Armisen R et al (2016) Immune DNA signature of T-cell infiltration in breast tumor exomes. Sci Rep 6(1):30064. https://doi.org/10.1038/srep30064 CrossRefPubMedPubMedCentral

13.

Brown SD, Raeburn LA, Holt RA (2015) Profiling tissue-resident T cell repertoires by RNA sequencing. Genome Med 7(1):125. https://doi.org/10.1186/s13073-015-0248-x CrossRefPubMedPubMedCentral

14.

Butler SN, Blanck G (2016) Immunoscoring by correlating MHC class II and TCR expression: high level immune functions represented by the KIRP dataset of TCGA. Cell Tissue Res 363(2):491–496. https://doi.org/10.1007/s00441-015-2261-1 CrossRefPubMed

15.

Redmond D, Poran A, Elemento O (2016) Single-cell TCRseq: paired recovery of entire T-cell alpha and beta chain transcripts in T-cell receptors from single-cell RNAseq. Genome Med 8(1):80. https://doi.org/10.1186/s13073-016-0335-7 CrossRefPubMedPubMedCentral

16.

Blachly JS, Ruppert AS, Zhao W, Long S, Flynn J, Flinn I, Jones J, Maddocks K, Andritsos L, Ghia EM, Rassenti LZ, Kipps TJ, de la Chapelle A, Byrd JC (2015) Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 112(14):4322–4327. https://doi.org/10.1073/pnas.1503587112 CrossRefPubMedPubMedCentral

17.

Li B, Li T, Wang B, Dou R, Zhang J, Liu JS, Liu XS (2017) Ultrasensitive detection of TCR hypervariable-region sequences in solid-tissue RNA-seq data. Nat Genet 49(4):482–483. https://doi.org/10.1038/ng.3820 CrossRefPubMed

18.

Samy MD, Tong WL, Yavorski JM, Sexton WJ, Blanck G (2017) T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-beta VDJ recombinations associates with a favorable oncologic outcome for bladder cancer. Cancer Immunol Immunother 66(3):403–410. https://doi.org/10.1007/s00262-016-1943-1 CrossRefPubMed

19.

Tu YN, Tong WL, Samy MD, Yavorski JM, Kim M, Blanck G (2017) Assessing microenvironment immunogenicity using tumor specimen exomes: co-detection of TcR-alpha/beta V(D)J recombinations correlates with PD-1 expression. Int J Cancer 140(11):2568–2576. https://doi.org/10.1002/ijc.30675 CrossRefPubMed

20.

Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado-Michaloud J, Chaume D, Lefranc MP (2006) IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res 34(Database issue):D781–D784. https://doi.org/10.1093/nar/gkj088 CrossRefPubMed

21.

Cosmi L, Annunziato F, Galli MIG, Maggi RME, Nagata K, Romagnani S (2000) CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol 30(10):2972–2979. https://doi.org/10.1002/1521-4141(200010)30:10<2972::AID-IMMU2972>3.0.CO;2-#

22.

Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, Thaiss CA, Reuben A, Livny J, Avraham R, Frederick DT, Ligorio M, Chatman K, Johnston SE, Mosher CM, Brandis A, Fuks G, Gurbatri C, Gopalakrishnan V, Kim M, Hurd MW, Katz M, Fleming J, Maitra A, Smith DA, Skalak M, Bu J, Michaud M, Trauger SA, Barshack I, Golan T, Sandbank J, Flaherty KT, Mandinova A, Garrett WS, Thayer SP, Ferrone CR, Huttenhower C, Bhatia SN, Gevers D, Wargo JA, Golub TR, Straussman R (2017) Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357(6356):1156–1160. https://doi.org/10.1126/science.aah5043 CrossRefPubMedPubMedCentral

23.

Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd, Casper ES et al (2012) Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw 10(6):703–713. https://doi.org/10.6004/jnccn.2012.0073 CrossRef

24.

Masso-Valles D, Jauset T, Serrano E, Sodir NM, Pedersen K, Affara NI, Whitfield JR, Beaulieu ME, Evan GI, Elias L, Arribas J, Soucek L (2015) Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma. Cancer Res 75(8):1675–1681. https://doi.org/10.1158/0008-5472.CAN-14-2852 CrossRefPubMed

25.

Gunderson AJ, Kaneda MM, Tsujikawa T, Nguyen AV, Affara NI, Ruffell B, Gorjestani S, Liudahl SM, Truitt M, Olson P, Kim G, Hanahan D, Tempero MA, Sheppard B, Irving B, Chang BY, Varner JA, Coussens LM (2016) Bruton tyrosine kinase-dependent immune cell cross-talk drives pancreas cancer. Cancer Discov 6(3):270–285. https://doi.org/10.1158/2159-8290.CD-15-0827 CrossRefPubMed

26.

Szekeres K, Koul R, Mauro J, Lloyd M, Johnson J, Blanck G (2014) An Oct-1-based, feed-forward mechanism of apoptosis inhibited by co-culture with Raji B-cells: towards a model of the cancer cell/B-cell microenvironment. Exp Mol Pathol 97(3):585–589. https://doi.org/10.1016/j.yexmp.2014.09.010 CrossRefPubMedPubMedCentral

27.

Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, Schmid MC, Sun P, Mose E, Bouvet M, Lowy AM, Valasek MA, Sasik R, Novelli F, Hirsch E, Varner JA (2016) Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression. Cancer Discov 6(8):870–885. https://doi.org/10.1158/2159-8290.CD-15-1346 CrossRefPubMedPubMedCentral

Titel: Recovery of Immunoglobulin VJ Recombinations from Pancreatic Cancer Exome Files Strongly Correlates with Reduced Survival
verfasst von: Jacob C. Kinskey
Yaping N. Tu
Wei Lue Tong
John M. Yavorski
George Blanck
Publikationsdatum: 05.02.2018
Verlag: Springer Netherlands
Erschienen in: Cancer Microenvironment / Ausgabe 1/2018
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI: https://doi.org/10.1007/s12307-018-0205-5

Springer Medizin

Recovery of Immunoglobulin VJ Recombinations from Pancreatic Cancer Exome Files Strongly Correlates with Reduced Survival

Abstract

Neu im Fachgebiet Onkologie

Erhöhte Mortalität bei postpartalem Brustkrebs

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

Update Onkologie

Springer Medizin

Abstract

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