Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 3/2017

19.12.2016 | Original Article

T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer

verfasst von: Mohammad D. Samy, Wei Lue Tong, John M. Yavorski, Wade J. Sexton, George Blanck

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, Hanada K, Almeida JR, Darko S, Douek DC, Yang JC, Rosenberg SA (2014) PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Investig 124:2246–2259CrossRefPubMedPubMedCentral Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, Hanada K, Almeida JR, Darko S, Douek DC, Yang JC, Rosenberg SA (2014) PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Investig 124:2246–2259CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Linnemann C, Heemskerk B, Kvistborg P, Kluin RJ, Bolotin DA, Chen X, Bresser K, Nieuwland M, Schotte R, Michels S, Gomez-Eerland R, Jahn L, Hombrink P, Legrand N, Shu CJ, Mamedov IZ, Velds A, Blank CU, Haanen JB, Turchaninova MA, Kerkhoven RM, Spits H, Hadrup SR, Heemskerk MH, Blankenstein T, Chudakov DM, Bendle GM, Schumacher TN (2013) High-throughput identification of antigen-specific TCRs by TCR gene capture. Nat Med 19:1534–1541CrossRefPubMed Linnemann C, Heemskerk B, Kvistborg P, Kluin RJ, Bolotin DA, Chen X, Bresser K, Nieuwland M, Schotte R, Michels S, Gomez-Eerland R, Jahn L, Hombrink P, Legrand N, Shu CJ, Mamedov IZ, Velds A, Blank CU, Haanen JB, Turchaninova MA, Kerkhoven RM, Spits H, Hadrup SR, Heemskerk MH, Blankenstein T, Chudakov DM, Bendle GM, Schumacher TN (2013) High-throughput identification of antigen-specific TCRs by TCR gene capture. Nat Med 19:1534–1541CrossRefPubMed
3.
Zurück zum Zitat 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 363:491–496CrossRefPubMed 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 363:491–496CrossRefPubMed
4.
Zurück zum Zitat Linnemann C, Mezzadra R, Schumacher TN (2014) TCR repertoires of intratumoral T-cell subsets. Immunol Rev 257:72–82CrossRefPubMed Linnemann C, Mezzadra R, Schumacher TN (2014) TCR repertoires of intratumoral T-cell subsets. Immunol Rev 257:72–82CrossRefPubMed
5.
Zurück zum Zitat 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 15:23–28PubMedPubMedCentral 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 15:23–28PubMedPubMedCentral
7.
Zurück zum Zitat Padovan E, Casorati G, Dellabona P, Meyer S, Brockhaus M, Lanzavecchia A (1993) Expression of two T cell receptor alpha chains: dual receptor T cells. Science 262:422–424CrossRefPubMed Padovan E, Casorati G, Dellabona P, Meyer S, Brockhaus M, Lanzavecchia A (1993) Expression of two T cell receptor alpha chains: dual receptor T cells. Science 262:422–424CrossRefPubMed
8.
Zurück zum Zitat Pal S, Bhattacharjee A, Ali A, Mandal NC, Mandal SC, Pal M (2014) Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism. J Inflamm (Lond) 11:23CrossRef Pal S, Bhattacharjee A, Ali A, Mandal NC, Mandal SC, Pal M (2014) Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism. J Inflamm (Lond) 11:23CrossRef
9.
Zurück zum Zitat Khawar MB, Abbasi MH, Sheikh N (2016) IL-32: a novel pluripotent inflammatory interleukin, towards gastric inflammation, gastric cancer, and chronic rhino sinusitis. Mediat Inflamm 2016:8413768CrossRef Khawar MB, Abbasi MH, Sheikh N (2016) IL-32: a novel pluripotent inflammatory interleukin, towards gastric inflammation, gastric cancer, and chronic rhino sinusitis. Mediat Inflamm 2016:8413768CrossRef
10.
Zurück zum Zitat Robbins PF (2015) T-cell receptor-transduced T cells: clinical experience. Cancer J 21:480–485CrossRefPubMed Robbins PF (2015) T-cell receptor-transduced T cells: clinical experience. Cancer J 21:480–485CrossRefPubMed
11.
Zurück zum Zitat Klarenbeek PL, Doorenspleet ME, Esveldt RE, van Schaik BD, Lardy N, van Kampen AH, Tak PP, Plenge RM, Baas F, de Bakker PI, de Vries N (2015) Somatic variation of T-cell receptor genes strongly associate with HLA class restriction. PLoS ONE 10:e0140815CrossRefPubMedPubMedCentral Klarenbeek PL, Doorenspleet ME, Esveldt RE, van Schaik BD, Lardy N, van Kampen AH, Tak PP, Plenge RM, Baas F, de Bakker PI, de Vries N (2015) Somatic variation of T-cell receptor genes strongly associate with HLA class restriction. PLoS ONE 10:e0140815CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Maletzki C, Schmidt F, Dirks WG, Schmitt M, Linnebacher M (2013) Frameshift-derived neoantigens constitute immunotherapeutic targets for patients with microsatellite-instable haematological malignancies: frameshift peptides for treating MSI + blood cancers. Eur J Cancer 49:2587–2595CrossRefPubMed Maletzki C, Schmidt F, Dirks WG, Schmitt M, Linnebacher M (2013) Frameshift-derived neoantigens constitute immunotherapeutic targets for patients with microsatellite-instable haematological malignancies: frameshift peptides for treating MSI + blood cancers. Eur J Cancer 49:2587–2595CrossRefPubMed
13.
Zurück zum Zitat Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199CrossRefPubMedPubMedCentral Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, Trebska-McGowan K, Wunderlich JR, Yang JC, Rosenberg SA (2016) Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med 22:433–438CrossRefPubMed Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, Trebska-McGowan K, Wunderlich JR, Yang JC, Rosenberg SA (2016) Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med 22:433–438CrossRefPubMed
15.
Zurück zum Zitat Westdorp H, Fennemann FL, Weren RD, Bisseling TM, Ligtenberg MJ, Figdor CG, Schreibelt G, Hoogerbrugge N, Wimmers F, de Vries IJ (2016) Opportunities for immunotherapy in microsatellite instable colorectal cancer. Cancer Immunol Immunother 65:1249–1259CrossRefPubMedPubMedCentral Westdorp H, Fennemann FL, Weren RD, Bisseling TM, Ligtenberg MJ, Figdor CG, Schreibelt G, Hoogerbrugge N, Wimmers F, de Vries IJ (2016) Opportunities for immunotherapy in microsatellite instable colorectal cancer. Cancer Immunol Immunother 65:1249–1259CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Silva-Santos B, Serre K, Norell H (2015) gammadelta T cells in cancer. Nat Rev Immunol 15:683–691CrossRefPubMed Silva-Santos B, Serre K, Norell H (2015) gammadelta T cells in cancer. Nat Rev Immunol 15:683–691CrossRefPubMed
Metadaten
Titel
T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer
verfasst von
Mohammad D. Samy
Wei Lue Tong
John M. Yavorski
Wade J. Sexton
George Blanck
Publikationsdatum
19.12.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 3/2017
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-016-1943-1

Weitere Artikel der Ausgabe 3/2017

Cancer Immunology, Immunotherapy 3/2017 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.