Immune cell infiltrates and prognosis in primary carcinoma of the lung
Introduction
The significance of a local immune reaction in the natural history of tumour progression has been debated for many years, and recently reviewed [1], [11]. In lung cancer, previous studies would suggest a beneficial prognostic effect of an enhanced immune response but methods of evaluating this response have varied widely, leading to difficulty in the comparison of results. Some made measurements of immune response using peripheral blood cells [6], [9], [15], [17], while others measured in vitro activity of immune cells extracted from human lung cancers [10], [13], [18]. Where the local immune cell infiltrate at the tumour site has been studied, there are few studies where there has been distinction between the different lymphocyte cell types present [2], [8], [12], [14], [16].
There is variation in the pattern of immune cell infiltration in tumours. In some cases the infiltrate is confined to the stroma (peritumoural), while in others immune cells are dispersed amongst the tumour cells (intratumoural). This has been studied in lung cancer, in H&E stained sections of tumour tissue and in relatively small numbers of cases [4], [7]. Lee and co-workers [7] found that peritumoural infiltration by lymphocytes was associated with a better prognosis while intratumoural infiltration was not. Another study described the prognostic benefit of peritumoural T- and B-lymphocytes. [14]
We describe the relationship between immune–chronic inflammatory cell infiltrates in lung cancer and survival in a large series of patients who had primary lung carcinoma resected. In a smaller group of these cases we describe the relationship of individual cell types in the tumour infiltrate, namely T-cells (CD3+), the CD8+ T-cell subset, B cells (CD79A+), natural killer cells (CD57+), macrophages (CD68+) and Langerhans cells (S100+), to patient survival. In addition the degree of intratumoural infiltration by each immune cell type has been measured and compared with survival.
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Materials and methods
The study group was a series of 710 fully reviewed and followed-up cases of primary lung cancer, representing all patients who had surgical resection as their treatment for lung cancer in Grampian region between 1980 and 1992. Some patients with stage III disease received postoperative radiotherapy. All cases had been histologically reviewed by two of us (KMK & MMK) and given a semi quantitative score (low/absent, moderate, or high) for the degree of chronic inflammation/immune cell infiltrate
General immune cell infiltration and survival
Groups of patients defined by different levels of semi-quantitatively assessed chronic inflammation–immune cell infiltration, as assessed on the H&E stained sections in 710 cases, showed no difference in patient survival. Not surprisingly, the same result was found for the smaller group subjected to detailed immunohistochemical study. The 5 year survival for all groups was 43% (Fig. 2).
Case mix of smaller study group
Of the 95 patients, 59 were male and 36 female. Ninety two patients had non-small cell carcinomas while three
Discussion
We have shown that, in a very large group of resected lung cancers, rough quantification of immune cell infiltration, ‘by eye’ on H&E stained sections, does not give useful prognostic information. Measurement of overall density of particular immune cell types in a tumour is equally uninformative. However, the presence of CD3+, S100+ and perhaps, CD57+ cells actually infiltrating amongst the tumour cells is associated with a more favourable prognosis for the patient.
Other studies have assessed
Acknowledgements
This study was partly funded by a grant from Aberdeen Royal Hospitals endowments. We are grateful to Professor S. Ralston and Dr R. van’t Hof for use of the image analyser.
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