PMC5754301_01
Chest computed tomography scans of a patient with undifferentiated non-small cell lung cancer. (a) Before treatment with nivolumab, a 28 mm tumor is seen in the left lower lobe of the lung. (b) After nine courses of nivolumab therapy, the diameter of the lung tumor increased to 55 mm. (c) After treatment with two courses of S-1, the lung tumor decreased to 20 mm in diameter.
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However, 18 months after the initiation of chemotherapy, the lesions progressed (Fig 1a), and she was administered nivolumab as third-line therapy. Despite nine cycles of nivolumab, disease progression and an increasing cough were evident (Fig 1b). The tumor rapidly regressed, resulting in a partial response six weeks later (Fig 1c). The patient's lung cancer has remained progression-free for five months.
Photomicrographs of a transbronchial biopsy specimen of a patient with undifferentiated non-small cell lung cancer. (a) Large, undifferentiated cancer cells are seen in the fibrous tissue (hematoxylin & eosin stain, original magnification 400x). (b) Immunohistochemical examination shows that > 90% of the tumor cells expressed programmed death ligand-1 at a high intensity (original magnification 400x).
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Histopathologic review of the transbronchial biopsy specimen at the time of diagnosis showed large, undifferentiated cancer cells (Fig 2a). Immunohistochemical examination indicated that > 90% of the tumor cells expressed PD-ligand 1 (PD-L1) (Fig 2b).
Immunohistochemical profiles of the tumor-infiltrating lymphocytes in a patient with undifferentiated non-small cell lung cancer. (a) CD3+ lymphocytes, (b) CD8+ cells, (c) CD4+ cells, (d) FOXP3+ regulatory T-cells, and (e) TIM-3+ cells are seen in the tumor stroma (original magnification 100x). The antibody clones used are as follows: CD3 (F7.2.38), CD8 (4B11), CD4 (4B12), FOXP3 (236A/E7), and TIM-3 (D5D5R).
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CD3+ T-lymphocytes were found in the tumor stroma (Fig 3a). Infiltration of CD8+ cells was more predominant than CD4+ cells (Fig 3b,c). FOXP3+ regulatory T-cells and cells positive for TIM-3+ were included in the tumor stroma (Fig 3d,e).
PMC5754301_02
Chest computed tomography scans of a patient with lung adenocarcinoma. Before treatment with nivolumab, (a) a 45 mm primary tumor is observed in the left lower lobe of the lung. (b) After six courses of nivolumab therapy, the primary lung tumor increased to 75 mm in diameter. (c) After two courses of carboplatin/albumin-bound paclitaxel therapy, the primary lung tumor decreased to a diameter of 25 mm.
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Eighteen months after the initiation of chemotherapy, the lung tumor enlarged (Fig 4a) and the serum CYFRA 21-1 level increased from 2.9 ng/mL to 4.5 ng/mL (reference value < 3.5 ng/mL). After six cycles of nivolumab, disease progression was evident (Fig 4b) and the CYFRA 21-1 level further increased to 6.4 mg/mL. Two months later, a partial response was achieved (Fig 4c).