Skip to main content

Advertisement

Log in

Analysis of the immunological microenvironment at the tumor site in patients with non-small cell lung cancer

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background and aims

Inactivation of tumor-infiltrating lymphocytes by immunomodulating cytokines shed by tumor cells into the tumor local microenvironment might be a potential escape strategy of various tumors from immune-immediate killing. Here, we provide an analysis of the cytokine profile at the tumor site in patients with non-small cell lung cancer (NSCLC).

Patients and methods

Using in situ hybridization (ISH), we determined the mRNA expression in lymphocytes and tumor cells for IL-2, INF-γ, IL-12 (p40), IL-18, IL-4, IL-10, TGF-β1, IL-1, IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, and TGF-α in five fresh pleural effusion samples and 18 tumor tissue samples of patients with NSCLC.

Results

In pleural effusion as well as in tumor tissue of NSCLC patients, the mRNA expression of IL-4, IL-10, TGF-α, and TGF-β1 was significantly higher than that of IL-2, IL-12, IL-18 and INF-γ. In contrast, the analysis of tuberculosis pleural effusion samples revealed lower mRNA levels for all cytokines and did not show any significant difference among them.

Conclusion

The predominant mRNA expression of type II and immunosuppressive cytokines in pleural effusion and tumor tissue of NSCLC patients mirrors an immunosuppressive state in the immunological microenvironment. The present study may, therefore, help to elucidate mechanisms of tumor escape and contribute to the development of an effective immunomodulatory treatment of NSCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A, B.
Fig. 2A, B.

Similar content being viewed by others

References

  1. Yano T, Hara N, Ichinose Y, Asoh H, Yokoyama H, Ohta M, Hata K (1994) Local recurrence after complete resection for non-small-cell carcinoma of the lung. Significance of local control by radiation treatment. J Thorac Cardiovasc Surg 107:8–12

    CAS  PubMed  Google Scholar 

  2. Yano T, Yokoyama H, Inoue T, Asoh H, Tayama K, Ichinose Y (1994) Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes. J Thorac Cardiovasc Surg 109:402–403

    Google Scholar 

  3. Yano T, Sugio K, Yamazaki K, Kase S, Yamaguchi M, Ondo K, Yoshino I, Sugimachi K (1999) Postoperative adjuvant adoptive immunotherapy with lymph node-LAK cells and IL-2 for pathologic stage I non-small cell lung cancer. Lung Cancer 26:143–148

    Article  CAS  PubMed  Google Scholar 

  4. Ioannides CG, Whiteside TL (1993) T cell recognition of human tumors: implications for molecular immunotherapy of cancer. Clin Immunol Immunopathol 66:91–106

    Article  CAS  PubMed  Google Scholar 

  5. Ochsenbein AF, Klenerman P, Karrer U, Ludewig B, Pericin M, Hengartner H, Zinkernagel RM (1999) Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci U S A 96: 2233–2238

    Google Scholar 

  6. De Vita F, Orditura M, Galizia G, Romano C, Roscigno A, Lieto E, Caltalano G (2000) Serum interleukin-10 level as a prognostic factor in advanced non-small cell lung cancer patients. Chest 117:365–373

    Article  PubMed  Google Scholar 

  7. Hatanaka H, Abe Y, Kamiya T, Morino F, Nagata J, Tokunaga T, Oshika Y, Suemizu H, Kijima H, Tsuchida T, Yamazaki H, Inoue H, Nakamura M, Ueyama Y (2000) Clinical implication of interleukin-10 induced by non-small cell lung cancer. Ann Oncol 11:815–819

    Article  CAS  PubMed  Google Scholar 

  8. Ganss R, Hanahan D (1998) Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes. Cancer Res 58:4673–4681

    CAS  PubMed  Google Scholar 

  9. Neuner A, Schindel M, Wildenberg U, Muley T, Lahm H, Fischer JR (2001) Cytokine secretion; clinical relevance of immunosuppression in non-small cell lung cancer. Lung Cancer 34[Suppl 2]:S79–82

    Google Scholar 

  10. Huang M, Wang J, Lee P, Sharma S, Mao JT, Meissner H, Uyemura K, Modlin R, Wollman J, Dubinett SM (1995) Human non-small cell lung cancer cells express a type 2 cytokine pattern. Cancer Res 55:3847–3853

    CAS  PubMed  Google Scholar 

  11. Liu J, Tian Z, Sun R (1998) The predominant expression of Th2 type cytokines in human tumor cells. Zhonghua Zhong Liu Za Zhi 20:105–107

    CAS  PubMed  Google Scholar 

  12. Asselin-Paturel C, Echchakir H, Carayol G, Gay F, Opolon P, Grunenw D, Chouaib S, Mami-Chouaib F (1998) Quantitative analysis of Th1, Th2 and TGF-beta 1 cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients. Int J Cancer 77:7–12

    Article  CAS  PubMed  Google Scholar 

  13. Chu Y, Hu HM, Winter H, Wood WJ, Doran T, Lashley D, Bashey J, Schuster J, Wood J, Lowe BA, Vetto JT, Weinberg AD, Puri R, Smith JW 2nd, Urba WJ, Fox BA (1999) Examining the immune response in sentinel lymph nodes of mice and men. Eur J Nucl Med 26[4 Suppl]:S50–S53

  14. Halak BK, Maguire HC Jr, Lattime EC (1999) Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site. Cancer Res 59:911–917

    CAS  PubMed  Google Scholar 

  15. Torre-Amione G, Beauchamp RD, Koeppen H, Park BH, Schreiber H, Moses HL, Rowley DA (1990) A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance. Proc Natl Acad Sci U S A 87:1486–1490

    Google Scholar 

  16. Takeuchi E, Yanagawa H, Suzuki Y, Shinkawa K, Ohmoto Y, Bando H, Sone S (2002) IL-12-induced production of IL-10 and interferon-γ by mononuclear cells in lung cancer-associated malignant pleural effusions. Lung Cancer 35:171–177

    Article  PubMed  Google Scholar 

  17. Rodolfo M, Zilocchi C, Accornero P, Cappetti B, Arioli I, Colombo MP (1999) IL-4 transduced tumor cell vaccine induces immunoregulatory type 2 CD8 T lymphocytes that cure lung metastases upon adoptive transfer. J Immunol 163:1923–1928

    CAS  PubMed  Google Scholar 

  18. Gunji Y, Tagawa M, Matsubara H, Takenaga K, Shimada H, Kondo F, Suzuki T, Nakajima K, Sugaya M, Asano T, Ochiai T, Isono K, Horitsu K, Kageyama H, Nakamura Y, Sakiyama S (1996) Antitumor effect induced by the expression of granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells. Cancer Lett 101:257–261

    CAS  PubMed  Google Scholar 

  19. Chang EY, Chen CH, Ji H, Wang TL, Hung K, Lee BP, Huang AY, Kurman RJ, Pardoll DM, Wu T (2000) Antigen-specific cancer immunotherapy using a GM-CSF secreting allogeneic tumor cell-based vaccine. Int J Cancer 86:725–730

    Article  CAS  PubMed  Google Scholar 

  20. Oshika Y, Nakamura M, Abe Y, Fukuchi Y, Yoshimura M, Itoh M, Ohnishi Y, Tokunaga T, Fukushima Y, Hatanaka H, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y (1998) Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF). Eur J Cancer 34:1958–1961

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

D.R. is a Chiles foundation visiting fellow.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rui Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, R., Rüttinger, D., Li, R. et al. Analysis of the immunological microenvironment at the tumor site in patients with non-small cell lung cancer. Langenbecks Arch Surg 388, 406–412 (2003). https://doi.org/10.1007/s00423-003-0416-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-003-0416-0

Keywords

Navigation