Chest
Original ResearchLung CancerHistologic Assessment of Tumor-Associated CD45+ Cell Numbers Is an Independent Predictor of Prognosis in Small Cell Lung Cancer
Section snippets
SCLC Cases
Ethical and institutional management approval for the study was obtained (LREC/2004/8/16). Sixty-four biopsy samples with primary lung SCLC from the years 1999 to 2001, for which sufficient residual material was available for study and for which clinical data were available, were identified from the pathology archives at the Royal Infirmary of Edinburgh (Table 1). The cases selected included four resection specimens, 14 core biopsies, 43 bronchial biopsies, and three mediastinal biopsies.
CD45 Counts and Overall Survival
Immunohistochemical staining of the sections highlighted the presence of CD45+ cells within the sections examined (Fig 1). The CD45 counts obtained for the 64 cases had an average of 37.6 positive cells per field, with a range of 2.8 to 127.4. The range and average value for each case counted is shown in Figure 2. Analysis of interobserver variability showed no statistical difference between the mean counts achieved by the observers, and differences in classification of sections as “high” or
Discussion
SCLC is a highly aggressive tumor with a poor prognosis that has frequently widely disseminated by the time of diagnosis. For many years, this type of lung cancer has been recognized as systemically influencing the function of the immune system. Although patients may respond to chemotherapy and/or radiotherapy, overall survival remains poor,4 and subsequent relapse and death are the usual outcome. Predictors of poor outcome and survival have centered on traditional factors, such as the stage of
Conclusions
The number of patients studied is relatively small and the historical data we had available did not include TNM staging, which has been found to provide better prognostic information than previous staging systems for SCLC.25 The data do strongly suggest that this is an area requiring further investigation. Many patients with SCLC clearly have mediastinal and hilar nodal enlargement at presentation. They are now frequently investigated using mediastinal sampling techniques, such as endobronchial
Acknowledgments
Author contributions: Dr Sethi is the guarantor of the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Mr Wang: contributed to the laboratory work, data analysis, editing, and approval of the manuscript.
Dr Hodkinson: contributed to the collection of patient data, laboratory work, data analysis, editing, and approval of the manuscript.
Dr McLaren: contributed to the laboratory work, data analysis, editing, and approval of the manuscript.
Dr
References (27)
- et al.
Estimates of the cancer incidence and mortality in Europe in 2006
Ann Oncol
(2007) - et al.
The epidemiology of lung cancer
Ann Oncol
(1999) - et al.
Could we expect to improve survival in small cell lung cancer?
Lung Cancer
(2007) - et al.
The value of prognostic factors in small cell lung cancer: results from a randomised multicenter study with minimum 5 year follow-up
Lung Cancer
(2003) - et al.
Selective suppression of cytokine secretion in patients with small-cell lung cancer
Ann Oncol
(1995) - et al.
Decrease of interleukin-2 secretion is a new independent prognostic factor associated with poor survival in patients with small-cell lung cancer
Ann Oncol
(1997) - et al.
Tumor-infiltrating T lymphocytes: friends or foes?
Lab Invest
(2006) - et al.
The inflammatory response within Dukes' B colorectal cancers: implications for progression of micrometastases and patient survival
Am J Gastroenterol
(2000) - et al.
Immune cell infiltrates and prognosis in primary carcinoma of the lung
Lung Cancer
(2000) - et al.
The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on non-small cell lung cancer
J Thorac Oncol
(2011)
The applicability of the proposed IASLC staging revisions to small cell lung cancer (SCLC) with comparison to the current UICC 6th TNM edition
J Thorac Oncol
Overview and state of the art in the management of lung cancer
Oncology (Williston Park)
Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database
J Clin Oncol
Cited by (54)
Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer
2021, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Proof of an active immune environment in SCLC has been described in a few analyses of patient samples. First, analysis of 64 SCLC tumors demonstrated that a wide range of CD45+ cells infiltrated the tumor, an average of 40 immune cells/field, and that high CD45+ counts were associated with a better prognosis.10 Evaluation of peripheral blood cells in 35 SCLC patients demonstrated a high CD4+ effector T cell to regulatory T cell ratio in patients with limited stage SCLC (LS-SCLC) versus ES-SCLC.11
Immune checkpoint blockade in small cell lung cancer
2019, Lung CancerCitation Excerpt :In a number of tumour types including non-small cell lung cancer (NSCLC), urothelial carcinoma and head and neck cancer, high TMB has been identified as a potential predictive marker, enriching for improved response to immune checkpoint blockade [18–20]. Prognosis of SCLC has also been linked with surrounding immune cell activity with worse survival found in patients with higher FOXP3 + T cells infiltrates [21] and improved survival associated with high CD45 + T cells counts [22]. Clinical evidence of the immunogenicity of SCLC has also been observed by the occurrence of paraneoplastic syndromes resulting from immune-mediated responses that suggest pathologic interplay between the tumour and the immune system [23–25].
A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer
2019, Lung CancerCitation Excerpt :It is known that smoking, the leading cause of SCLC, contributes to the high mutation rate characteristic of SCLC [15,16]. In addition, the increased levels of tumor-infiltrate lymphocytes have been shown to be associated with the prolonged survival in SCLC [17]. Therefore, therapeutic intervention with immunotherapy seems to be a reasonable option for SCLC patients.
PTPRC functions as a prognosis biomarker in the tumor microenvironment of cutaneous melanoma
2023, Scientific Reports
Funding/Support: This work was funded by the Medical Research Council (United Kingdom) and the Chief Scientist's Office (Scotland) [Grant CZB/4/504].
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.
- 1
Drs Wallace and Sethi contributed equally to this work.