Skip to main content

Advertisement

Log in

Local and systemic immunity predict survival in patients with pulmonary sarcomatoid carcinoma

  • Short Communication
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Pulmonary sarcomatoid cancer (PSC) is a rare, aggressive subtype of non-small cell lung cancer, and measures of local and systemic immunity as biomarkers are incompletely known. We performed this study to characterize the leukocyte composition within the tumor, stroma, and peripheral blood in patients with PSC and correlated our findings with overall survival. Tissue from 30 patients diagnosed with PSC was evaluated by IHC for the presence of CD3+, CD14+, and CD19+ cells and PD-L1 expression. A lymphocyte-to-monocyte ratio (LMR) was calculated for the tumor microenvironment (TME) and peripheral blood. Survival analyses were performed based on IHC scores or groups defined by receiver operating characteristic curve cutoffs. CD3+ and CD14+ cells were found throughout the TME. CD19+ cells were almost exclusive to the stroma and correlated with superior overall survival (HR 0.40, 95% CI 0.21–0.72, p = 0.003). Most patients expressed PD-L1 on the tumor and/or the infiltrating immune cells, but neither the presence nor PD-L1 expression level impacted survival. A more prolific immune infiltration of the TME was associated with improved survival (HR 0.82, 95% CI 0.70–0.98, p = 0.029). PSC patients with a TME LMR ≥1.2 had a median survival of 1598 versus 488 days for a TME LMR <1.2 (p = 0.010). In the peripheral blood, an LMR ≥2.3 was associated with improved median survival (1579 vs. 332 days, p < 0.001). Our data demonstrate multiple measures of the local and systemic immunity are associated with patient survival in PSC.

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. 1
Fig. 2

References

  1. Dellon AL, Potvin C, Chretien PB. Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma. J Surg Oncol. 1979;12(3):253–61.

    Article  CAS  PubMed  Google Scholar 

  2. Wesselius LJ, et al. Lymphocyte subsets in lung cancer. Chest. 1987;91(5):725–9.

    Article  CAS  PubMed  Google Scholar 

  3. Teramukai S, et al. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45(11):1950–8.

    Article  PubMed  Google Scholar 

  4. Kumagai S, et al. Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma. Lung Cancer. 2014;85(3):457–64.

    Article  PubMed  Google Scholar 

  5. Hu P, et al. Prognostic significance of systemic inflammation-based lymphocyte-monocyte ratio in patients with lung cancer: based on a large cohort study. PLoS ONE. 2014;9(10):e108062.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Johnson SK, et al. Immune cell infiltrates and prognosis in primary carcinoma of the lung. Lung Cancer. 2000;27(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  7. Ruffini E, et al. Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ann Thoracic Surg. 2009;87(2):365–71 (discussion 371–2).

    Article  Google Scholar 

  8. Goc J, et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Can Res. 2014;74(3):705–15.

    Article  CAS  Google Scholar 

  9. Wakabayashi O, et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci. 2003;94(11):1003–9.

    Article  CAS  PubMed  Google Scholar 

  10. Hiraoka K, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer. 2006;94(2):275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Al-Shibli KI, et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14(16):5220–7.

    Article  CAS  PubMed  Google Scholar 

  12. Kawai O, et al. Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113(6):1387–95.

    Article  CAS  PubMed  Google Scholar 

  13. Pelletier MP, et al. Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis. Can J Surg. 2001;44(3):180–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Germain C, et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am J Respir Crit Care Med. 2014;189(7):832–44.

    Article  CAS  PubMed  Google Scholar 

  15. Suzuki K, et al. Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(4):490–8.

    Article  CAS  Google Scholar 

  16. Yendamuri S, et al. Outcomes of sarcomatoid carcinoma of the lung: a surveillance, epidemiology, and end results database analysis. Surgery. 2012;152(3):397–402.

    Article  PubMed  Google Scholar 

  17. Kim S, et al. Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: comparison of sarcomatous and carcinomatous areas. Eur J Cancer. 2015;51:2698–707.

    Article  CAS  PubMed  Google Scholar 

  18. Vieira T, et al. Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages. Lung Cancer. 2016;98:51–8.

    Article  PubMed  Google Scholar 

  19. Terra SBSP, et al. Immunohistochemical study of 36 cases of pulmonary sarcomatoid carcinoma—sensitivity of TTF-1 is superior to napsin. Hum Pathol. 2014;45(2):294–302.

    Article  CAS  PubMed  Google Scholar 

  20. Mansfield AS, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thoracic Oncol Off Publ Int Assoc Study Lung Cancer. 2014;9(7):1036–40.

    CAS  Google Scholar 

  21. Krikman TW. Statistics to use. 1996 [cited 2015 October 16]; Available from http://www.physics.csbsju.edu/stats/.

  22. Topalian Suzanne L, Drake Charles G, Pardoll Drew M. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Velcheti V, Rimm DL, Schalper KA. Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1). J Thoracic Oncol. 2013;8(6):803–5.

    Article  CAS  Google Scholar 

  24. Gounant V, et al. Nivolumab-induced organizing pneumonitis in a patient with lung sarcomatoid carcinoma. Lung Cancer. 2016;99:162–5.

    Article  CAS  PubMed  Google Scholar 

  25. Raveglia F, et al. Personal experience in surgical management of pulmonary pleomorphic carcinoma. Ann Thoracic Surg. 2004;78(5):1742–7.

    Article  Google Scholar 

  26. Bae H-M, et al. Palliative chemotherapy for pulmonary pleomorphic carcinoma. Lung Cancer. 2007;58(1):112–5.

    Article  PubMed  Google Scholar 

  27. Hong J, et al. The role of palliative chemotherapy for advanced pulmonary pleomorphic carcinoma. Med Oncol. 2009;26(3):287–91.

    Article  CAS  PubMed  Google Scholar 

  28. Chaft JE, et al. Clinical outcomes with perioperative chemotherapy in sarcomatoid carcinomas of the lung. J Thoracic Oncol. 2012;7(9):1400–5.

    Article  Google Scholar 

  29. Vieira T, et al. Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma. J Thoracic Oncol. 2013;8(12):1574–7.

    Article  CAS  Google Scholar 

  30. Nishijima TF, et al. Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev. 2015;41(10):971–8.

    Article  PubMed  Google Scholar 

  31. Li ZM, et al. Blood lymphocyte-to-monocyte ratio identifies high-risk patients in diffuse large B-cell lymphoma treated with R-CHOP. PLoS ONE. 2012;7(7):e41658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Koh YW, et al. The ratio of the absolute lymphocyte count to the absolute monocyte count is associated with prognosis in Hodgkin’s lymphoma: correlation with tumor-associated macrophages. Oncologist. 2012;17(6):871–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Porrata LF, et al. Peripheral blood absolute lymphocyte/monocyte ratio during rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone treatment cycles predicts clinical outcomes in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014;55(12):2728–38.

    Article  CAS  PubMed  Google Scholar 

  34. Fujiwara Y, et al. Postoperative peripheral absolute blood lymphocyte-to-monocyte ratio predicts therapeutic outcome after pancreatic resection in patients with pancreatic adenocarcinoma. Anticancer Res. 2014;34(9):5163–8.

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by an intramural grant from the Department of Laboratory Medicine and Pathology, Mayo Clinic.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Allan Dietz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Mayo Clinic Institutional Review Board and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Human and animal rights

This article does not contain any studies with animals performed by any of the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schenk, E., Boland, J., Mansfield, A. et al. Local and systemic immunity predict survival in patients with pulmonary sarcomatoid carcinoma. Med Oncol 34, 140 (2017). https://doi.org/10.1007/s12032-017-1000-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-017-1000-8

Keywords

Navigation