Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 9/2010

01.09.2010 | Original Paper

Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients

verfasst von: Hyunji Lee, Ji Hyun Kim, Sung Yeun Yang, Jihye Kong, Minkyung Oh, Dae Hoon Jeong, Jae-il Chung, Ki Beom Bae, Jin Yong Shin, Kwan Hee Hong, Inhak Choi

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2010

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To associate the global gene expression of B7/CD28 family transcripts with pathologic features of colon cancer, we determined the B7/CD28 family transcripts in peripheral blood mononuclear cells (PBMCs) from normal subjects and patients with adenomatous polyps and colon cancer, and correlated the results with pathologic features of colon cancer.

Methods

PBMCs from age-matched normal subjects and patients with adenomatous polyps and colon cancer were analyzed for peripheral blood transcripts (PBTs) of B7/CD28 family using real-time PCR. Differences in expression levels of B7/CD28 PBTs across all cancer stages and between colon cancer patients with or without microscopic lymphovascular invasion (LVI) were analyzed.

Results

The results showed a significant upregulation of PBTs of co-inhibitory molecules such as B7-H3 and PD-1 and a significant PBT downregulation of co-stimulatory molecules including CD28 and ICOS in colon cancer patients. Furthermore, the increase of B7-H3 PBT was strongly associated with tumor invasion (P = 0.025) and advanced TNM stages (P = 0.019), whereas the decline of co-stimulatory ligand B7-H2 PBT was related to regional lymph node metastasis (P = 0.028) and aggressive tumor invasion (P = 0.031). In addition, the ratios of PBT expression of CD28 family to B7 family such as CTLA-4 to B7-H2 and PD-1 to B7-H2 were significantly higher in colon cancer patients with microscopic LVI than in those without LVI (P = 0.001 and P = 0.016, respectively).

Conclusions

Our results suggest that B7/CD28 family PBTs may serve as valuable markers reflecting the pathological features of colon cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH et al (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687CrossRefPubMed Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH et al (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687CrossRefPubMed
Zurück zum Zitat Boorjian SA, Sheinin Y, Crispen PL, Farmer SA, Lohse CM, Kuntz SM et al (2008) T cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin Cancer Res 14:4800–4808CrossRefPubMed Boorjian SA, Sheinin Y, Crispen PL, Farmer SA, Lohse CM, Kuntz SM et al (2008) T cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin Cancer Res 14:4800–4808CrossRefPubMed
Zurück zum Zitat Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS et al (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 171:4650–4654PubMed Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS et al (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 171:4650–4654PubMed
Zurück zum Zitat Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X et al (2008) Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res 14:5150–5157CrossRefPubMed Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X et al (2008) Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res 14:5150–5157CrossRefPubMed
Zurück zum Zitat Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567CrossRefPubMed Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567CrossRefPubMed
Zurück zum Zitat Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB et al (2002) Tumor-associated B7-H1 promotes T cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800PubMed Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB et al (2002) Tumor-associated B7-H1 promotes T cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800PubMed
Zurück zum Zitat Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548CrossRefPubMed Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548CrossRefPubMed
Zurück zum Zitat Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096PubMed Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096PubMed
Zurück zum Zitat Jeong HY, Lee YJ, Seo SK, Lee SW, Park SJ, Lee JN, Choi I et al (2008) Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell immunity in chronic hepatitis C infection. J Leukoc Biol 83:755–764CrossRefPubMed Jeong HY, Lee YJ, Seo SK, Lee SW, Park SJ, Lee JN, Choi I et al (2008) Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell immunity in chronic hepatitis C infection. J Leukoc Biol 83:755–764CrossRefPubMed
Zurück zum Zitat Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10:5094–5100CrossRefPubMed Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10:5094–5100CrossRefPubMed
Zurück zum Zitat Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P et al (2006) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203:871–881CrossRefPubMed Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P et al (2006) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203:871–881CrossRefPubMed
Zurück zum Zitat Loos M, Giese NA, Kleeff J, Giese T, Gaida MM, Bergmann F et al (2008) Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer. Cancer Lett 268:98–109CrossRefPubMed Loos M, Giese NA, Kleeff J, Giese T, Gaida MM, Bergmann F et al (2008) Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer. Cancer Lett 268:98–109CrossRefPubMed
Zurück zum Zitat Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N et al (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 11:2947–2953CrossRefPubMed Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N et al (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 11:2947–2953CrossRefPubMed
Zurück zum Zitat Prasad DV, Nguyen T, Li Z, Yang Y, Duong J, Wang Y et al (2004) Murine B7-H3 is a negative regulator of T cells. J Immunol 173:2500–2506PubMed Prasad DV, Nguyen T, Li Z, Yang Y, Duong J, Wang Y et al (2004) Murine B7-H3 is a negative regulator of T cells. J Immunol 173:2500–2506PubMed
Zurück zum Zitat Roth TJ, Sheinin Y, Lohse CM, Kuntz SM, Frigola X, Inman BA et al (2007) B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res 67:7893–7900CrossRefPubMed Roth TJ, Sheinin Y, Lohse CM, Kuntz SM, Frigola X, Inman BA et al (2007) B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res 67:7893–7900CrossRefPubMed
Zurück zum Zitat Simon I, Katsaros D, Rigault de la Longrais I, Massobrio M, Scorilas A, Kim NW et al (2007) B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression. Gynecol Oncol 106:334–341CrossRefPubMed Simon I, Katsaros D, Rigault de la Longrais I, Massobrio M, Scorilas A, Kim NW et al (2007) B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression. Gynecol Oncol 106:334–341CrossRefPubMed
Zurück zum Zitat Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS et al (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66:3381–3385CrossRefPubMed Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS et al (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66:3381–3385CrossRefPubMed
Zurück zum Zitat Wang L, Fraser CC, Kikly K, Wells AD, Han R, Coyle AJ et al (2005) B7-H3 promotes acute and chronic allograft rejection. Eur J Immunol 35:428–438CrossRefPubMed Wang L, Fraser CC, Kikly K, Wells AD, Han R, Coyle AJ et al (2005) B7-H3 promotes acute and chronic allograft rejection. Eur J Immunol 35:428–438CrossRefPubMed
Zurück zum Zitat Wu CP, Jiang JT, Tan M, Zhu YB, Ji M, Xu KF et al (2006) Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol 12:457–459PubMed Wu CP, Jiang JT, Tan M, Zhu YB, Ji M, Xu KF et al (2006) Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol 12:457–459PubMed
Zurück zum Zitat Yao S, Chen L (2006) Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade. Trends Mol Med 12:244–246CrossRefPubMed Yao S, Chen L (2006) Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade. Trends Mol Med 12:244–246CrossRefPubMed
Zurück zum Zitat Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA et al (2007) B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA 104:19458–19463CrossRefPubMed Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA et al (2007) B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA 104:19458–19463CrossRefPubMed
Metadaten
Titel
Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients
verfasst von
Hyunji Lee
Ji Hyun Kim
Sung Yeun Yang
Jihye Kong
Minkyung Oh
Dae Hoon Jeong
Jae-il Chung
Ki Beom Bae
Jin Yong Shin
Kwan Hee Hong
Inhak Choi
Publikationsdatum
01.09.2010
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0800-4

Weitere Artikel der Ausgabe 9/2010

Journal of Cancer Research and Clinical Oncology 9/2010 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.