ABSTRACT
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Humans , Nivolumab/pharmacology , Nivolumab/therapeutic use , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/metabolism , Retrospective Studies , Mesothelioma, Malignant/drug therapy , Mesothelioma/drug therapy , Mesothelioma/pathology , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
The patient was a 67-year-old male undergoing maintenance hemodialysis due to chronic renal failure caused by diabetic nephropathy. A left upper lobe resection was carried out for non-small cell lung cancer of the left upper lobe. It was histologically confirmed as pleomorphic carcinoma pT3N0M0, Stage â ¡B. He suffered a relapse with multiple metastases occurring in both lungs 3 months following surgery. The PD-L1 tumor proportion score(TPS)was 90%, indicating a high level of expression; 200mg of pembrolizumab was administered every 3 weeks on non-dialysis days. Two courses of administration achieved a partial response. A total of 17 courses were administered until discontinuation due to drug-induced lung injury.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma , Lung Neoplasms , Aged , Antibodies, Monoclonal, Humanized , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung/metabolism , Lung/pathology , Lung Neoplasms/pathology , Male , Neoplasm Recurrence, Local , Renal DialysisABSTRACT
Cases of drug-induced lung injury caused by tamoxifen are rare. A 74-year-old man underwent surgery for the treatment of right breast cancer; tamoxifen was administered as an adjuvant therapy after surgery. The patient developed cough and dyspnea and chest computed tomography showed ground glass opacification in the lower lobe of the right lung. He was diagnosed with tamoxifen-induced lung injury. The diagnosis was made based on the exclusion of other causes and recurrence with the re-administration of tamoxifen. Physicians should therefore be aware of the potential for the development of tamoxifen-induced lung injury.
