Peripheral CD8(+) T cell proliferation is prognostic for patients with advanced thoracic malignancies

Our plain-English summary of Peripheral CD8(+) T cell proliferation is prognostic for patients with advanced thoracic malignancies, by M.J. McCoy, A.K. Nowak, R.G. van der Most, et al (Cancer Immunology, Immunotherapy, 2013).

The study

• Authors: M.J. McCoy, A.K. Nowak, R.G. van der Most, I.M. Dick, R.A. Lake
• Journal: Cancer Immunology, Immunotherapy
• Published: 2013;62(3):529-39
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

There is a complex interplay between the immune system and a developing tumor that is manifest in the way that the balance of T cell subsets in the local tumor environment reflects clinical outcome. Tumor infiltration by CD8(+) T cells and regulatory T cells (Treg) is associated with improved and reduced survival, respectively, in many cancer types. However, little is known of the prognostic value of immunological parameters measured in peripheral blood. In this study, peripheral CD8(+) T cells and Treg from 43 patients with malignant mesothelioma or advanced non-small-cell lung cancer scheduled to commence palliative chemotherapy were assessed by flow cytometry and evaluated for association with patient survival. Patients had a higher proportion of peripheral Treg, proliferating CD8(+) T cells and CD8(+) T cells with an activated effector phenotype compared with age-matched healthy controls. Higher proportions of Treg and proliferating CD8(+) T cells were both associated with poor survival in univariate analyses (hazard ratio [HR] 3.81, 95 % CI 1.69-8.57; p < 0.01 and HR 2.86, 95 % CI 1.26-6.50; p < 0.05, respectively). CD8(+) T cell proliferation was independently predictive of reduced survival in multivariate analysis (HR 2.58, 95 % CI 1.01-6.61; p < 0.05). These findings suggest that peripheral CD8(+) T cell proliferation can be a useful prognostic marker in patients with thoracic malignancies planned for palliative chemotherapy.

In plain English

This study measured blood immune cells in 43 patients with malignant mesothelioma (27) or advanced non-small-cell lung cancer (16) before palliative chemotherapy, comparing them with healthy volunteers. It did not study asbestos exposure. Patients had higher proportions of dividing ('proliferating') CD8+ T cells, activated CD8+ T cells and regulatory T cells (Treg) than healthy controls. Of 18 patients tested, 15 responded to a pool of virus-derived peptides, and their share of responding CD8+ T cells was similar to controls'. Patients with higher Treg or proliferating CD8+ T cell levels had shorter survival. Median survival was 5.3 versus 10.8 months by Treg level, and 7.9 versus 20.9 months by proliferating CD8+ T cell level, with cut-offs set where the link was strongest. After adjusting for other factors, only proliferating CD8+ T cells stayed linked to survival (hazard ratio 2.58, 95% CI 1.01 to 6.61). The authors concluded this could be a useful prognostic marker if confirmed in an independent study. They named as weaknesses the mixed disease types, varied chemotherapy, and tumor staging that could not be compared across the two cancers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Observational study: blood samples taken before chemotherapy, analyzed by flow cytometry, compared with healthy controls, and related to survival during follow-up
• Who was studied: 43 patients (27 malignant mesothelioma, 16 non-small-cell lung cancer; 9 female; mean age 65) about to start platinum-based chemotherapy. The authors were based in Western Australia; study dates are not given. Controls were 27 healthy people: 14 university volunteers and 13 patients' spouses. Only the 15 controls aged 50 or over were used for the proliferating and effector cell comparisons.
• Exposure: Asbestos exposure was not studied. The factors examined were blood immune measures: proportions of proliferating and activated (effector) CD8+ T cells, regulatory T cells (Treg) and proliferating Treg.
• Main results:
  • Patients had higher proportions of Treg, proliferating CD8+ T cells and CD8+ T cells with an activated effector phenotype than healthy controls.
  • Of 18 patients tested, responses to a pool of virus-derived peptides (from cytomegalovirus, Epstein-Barr virus and influenza virus) were detected in 15. In those responding patient samples, the proportion of virus-specific CD8+ T cells ranged from 5 to 53% (mean 38%), which the authors described as comparable to controls (11 to 52%, mean 36%).
  • In univariate analysis, a higher proportion of Treg was associated with poorer survival (HR 3.81, 95% CI 1.69 to 8.57, p less than 0.01), as was a higher proportion of proliferating CD8+ T cells (HR 2.86, 95% CI 1.26 to 6.50, p less than 0.05).
  • Median survival was 5.3 months in patients whose Treg made up 7.5% or more of CD4+ T cells (n = 9), versus 10.8 months in those with fewer Treg (n = 33). It was 7.9 months in patients with 2.9% or more of CD8+ T cells proliferating (n = 28), versus 20.9 months below 2.9% (n = 14).
  • In multivariate analysis, the proportion of proliferating CD8+ T cells remained independently associated with survival (HR 2.58, 95% CI 1.01 to 6.61, p less than 0.05). Treg did not remain significant (HR 2.40, 95% CI 0.94 to 6.17, p = 0.069), and no clinical variables remained significant.
  • No immunological or clinical variable predicted time to progression or best radiological response.
• The authors' conclusion: The authors concluded that peripheral CD8+ T cell proliferation was prognostic for poorer survival and, if validated in an independent study, may be a useful prognostic marker in patients with mesothelioma and advanced non-small-cell lung cancer receiving palliative chemotherapy. They proposed that increased immune activity may reflect more advanced disease.
• Limitations the authors state:
  • The patient group combined two disease types, mesothelioma and non-small-cell lung cancer.
  • Because nearly all patients (93%) went on to chemotherapy, the findings may be predictive of treatment outcome rather than prognostic.
  • Patients received different chemotherapy regimens.
  • Tumor staging could not be compared between mesothelioma and lung cancer patients, and no other measure of tumor burden was available. As a result, no direct measure of disease extent could be included in the multivariate analysis.
  • Patient numbers were too small to analyze survival separately by disease.
  • The authors could not determine whether the activated T cells were directed against the tumor.
  • No correction for multiple comparisons was made.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Palliative Care, Chemotherapy, Hazard Ratio, Multivariate Analysis.

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