Increased frequency of circulating invariant natural killer T cells in malignant pleural mesothelioma patients

Our plain-English summary of Increased frequency of circulating invariant natural killer T cells in malignant pleural mesothelioma patients, by E. Altomare, S. Fallarini, G. Biaggi, et al (Cancer Biology & Therapy, 2012).

The study

• Authors: E. Altomare, S. Fallarini, G. Biaggi, E. Gattoni, M. Botta, G. Lombardi
• Journal: Cancer Biology & Therapy
• Published: 2012;13(9):702-11
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Invariant natural killer T (iNKT) cells are a distinct subset of human T cells, which expresses an invariant T cell receptor Vα24 Jα18 and recognizes glycolipid antigens in the context of CD1d molecules. iNKT cells exert pivotal regulatory roles in many immune responses, including antitumor immune responses. Alterations in iNKT cell frequency, phenotype, and activation state have been reported in cancer patients. No data are available on the iNKT cells in malignant pleural mesothelioma (MPM), a rare, but very aggressive, malignancy of the pleura with a very poor prognosis. Here, we studied the frequency, phenotype, and cytokine profile of circulating iNKT cells in MPM patients, and correlated results with tumor histological types (epithelioid, sarcomatoid, biphasic) and clinical stages (I-III). We found that the iNKT cell frequency was significantly increased in MPM patients with epithelioid and sarcomatoid types in comparison with healthy volunteers (HV); only three biphasic mesotheliomas were available in this study, thus no conclusions can be drawn for this MPM type. The increased frequency significantly correlates with the clinical stage of tumor with the highest value at the stage III in both epithelioid and sarcomatoid subtypes. According to the histological types, we measured changes in the frequencies of CD4⁺ CD8⁺ (DP) and CD4⁻CD8⁻ (DN), but not in the cytokine profiles (IFN-γ/IL-4 expression). These results demonstrate that the frequency of iNKT cells is increased in MPM patients and that this increase correlates with MPM type and stage.

In plain English

This Italian study measured invariant natural killer T (iNKT) cells, a rare immune cell type, in the blood of 30 malignant pleural mesothelioma patients from Casale Monferrato. It compared them with 22 asbestos-unexposed healthy volunteers of similar age and sex. Asbestos exposure was occupational in 8 patients, indirect in 19 and not reported in 3. Across all patients, the increase over volunteers was a trend that was not statistically significant. iNKT cell frequency was significantly higher than in volunteers in the 22 epithelioid patients (+66 ± 9%). The 5 sarcomatoid patients also showed a significant increase (+78 ± 7%), and the 3 biphasic cases showed no difference, but the authors said both groups were too small for conclusions. Among epithelioid patients, the increase was significant at stage III (+88 ± 13%). Stage IV values were lower and not significant. After laboratory stimulation, the share of iNKT cells producing IFNγ or IL-4 did not differ between groups. The authors concluded that the increase seems correlated with disease type and severity. They said results need confirming in more patients and might partly reflect overestimation from their cell-identification method.

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: Clinical study comparing blood samples from mesothelioma patients with those from age- and gender-matched healthy volunteers (laboratory flow cytometry analysis)
• Who was studied: 30 patients with malignant pleural mesothelioma (23 men, 7 women; mean age 62.5, range 41 to 80). By histology: 22 epithelioid, 3 biphasic, 5 sarcomatoid. By stage: I (3), II (5), III (15), IV (7). All came from Casale Monferrato, Italy. They were compared with 22 healthy volunteers (19 men, 3 women; mean age 58.5, range 44 to 76) who did not live in the patients' area. No study dates are given.
• Exposure: The condition studied was malignant pleural mesothelioma. Among patients, asbestos exposure was occupational in 8, indirect in 19 (labelled 'environmental' in Table 1) and not reported in 3. Healthy volunteers were not exposed to asbestos. No fiber types are specified.
• Main results:
  • All 30 patients compared with healthy volunteers: a trend toward increased iNKT cell frequency that was not statistically significant (figures printed as 0.02 vs. 0.1%).
  • Epithelioid patients had a significant increase in iNKT cell frequency of +66 ± 9% (p less than 0.05). Sarcomatoid patients had an increase of +78 ± 7% (p less than 0.01).
  • Despite the reported sarcomatoid result, the authors' Discussion said no conclusions can be drawn for the biphasic (n = 3) or sarcomatoid (n = 5) groups.
  • No difference was observed between biphasic patients and healthy volunteers. The authors stated that with only three biphasic cases, no conclusions can be drawn for this type.
  • In epithelioid patients, the share of double-negative (CD4-CD8-) iNKT cells was significantly lower than in volunteers (20 vs. 25%, p less than 0.05).
  • In epithelioid patients, the share of double-positive (CD4+CD8+) iNKT cells was significantly higher than in volunteers (28 vs. 18%).
  • Epithelioid patients at stage III had a significant increase in iNKT cell frequency of +88 ± 13% (p less than 0.01).
  • Epithelioid patients at stage IV had a lower frequency that was not significant.
  • No statistical analysis by stage was possible for sarcomatoid patients because there were too few cases.
  • After laboratory stimulation, the percentages of iNKT cells positive for IFNγ or IL-4 did not differ between patients and volunteers. This also held when each histological subtype was considered separately.
  • Smoking and non-smoking subjects did not differ in iNKT cell frequency (data not shown).
• The authors' conclusion: The authors concluded that the study shows, for the first time, a significant increase in circulating iNKT cells in malignant pleural mesothelioma patients. They concluded that this increase seems to be correlated with the type and severity of disease.
• Limitations the authors state:
  • The results need to be confirmed in a larger number of patients.
  • Differences in the method used to identify (gate) iNKT cells could have led to overestimating their numbers.
  • No conclusions can be drawn for the biphasic (n = 3) and sarcomatoid (n = 5) groups.
  • The very low numbers of sarcomatoid and biphasic patients may explain the lack of findings in those groups.
  • Few patients had stage IV tumors, so those results should be interpreted with caution.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleura, Prognosis, Cytokine, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

Related studies

• Lymphocyte subsets in subjects exposed to asbestos: changes in circulating natural killer cells — N. al Jarad, M. Macey, et al. (1992)
• Lymphocyte subsets in subjects exposed to asbestos: changes in circulating natural killer cells — P.J. Borm, P.F. Schins (1993)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)
• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)

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