PMC8207139_01
Computed tomography (CT) scans of the thorax of the patient. (A) CT scan before the treatment. (B) Image of the best response of pembrolizumab therapy. (C) Image of progression of pembrolizumab therapy and before atezolizumab therapy. (D) Image of best response of atezolizumab therapy. CR, complete response; SD, stable disease; PD, progressive disease.
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The chest computed tomography scan was performed, which revealed a solid nodule in the right lower lung ( Figure 1A ). The patient then received one cycle of pembrolizumab combined with recombinant human endostatin for malignant pleural effusion, after which she continued with pembrolizumab 200 mg every three weeks since June 2019 with a stable disease status ( Figure 1B ). Pembrolizumab treatment stopped in July 2020 when a newly emerged left hilar mass shadow was found in the patient ( Figure 1C ). The patient experienced a complete response to atezolizumab based on the 5-month scan ( Figure 1D ).
Immunohistochemical examination: (A) Pathologic findings from the right lower lobe lesion at the time of initial diagnosis showed adenocarcinoma (hematoxylin and eosin [H&E] staining), with positive immunohistochemical staining for CK7, Napsin-A, TTF1 and PD-L1. (B) Pathologic finding from the intraluminal lesion in the left bronchus at the time of progression showed small cell lung cancer (H&E), with positive immunohistochemical staining for CD56, synaptophysin and Ki-67, and negative staining for PD-L1.
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Pathologic analysis of the postoperative specimens confirmed infiltrating adenocarcinoma ( Figure 2A ) and systemic work-up staged the tumour as cT4N2M1a. At that time, the biopsy specimen showed high PD-L1 expression with a tumor proportion score (TPS) of 80% by immunohistochemistry (Dako 22C3) ( Figure 2A ). Subsequently, the bronchoscopic biopsy sample from the left lung hilar mass showed tumor cells positive for synaptophysin, CD56, and Ki-67 (80%), which were consistent with SCLC, and negative for PD-L1 ( Figure 2B ).
Mutations and tumor microenvironments. (A) Overlap of non-silent mutations of adenocarcinoma (T1) and small cell lung cancer (T2) samples from the same patient. (B) Fractions of infiltrating cells. (C) CD8+ T cells of T1. (D) CD8+ T cells of T2. (E) CD4+ T cells of T1. (F) CD4+ T cells of T2.
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NF1 mutation was detected. No shared mutations were detected between T1 (520-target panel sequencing) and T2 (WES) from the same patient ( Figure 3A ), and the two lesions contain different oncogenic driver mutations, suggesting that these two lesions might be from separate primary lung cancers. T1, T2 exhibited less immune infiltrating cells, including CD8+ T cells and B cells, and lower score of immune and microenvironment ( Figure 3B ). The different distributions of CD8+ and CD4+ T cells between two tissues were validated by immunohistology ( Figures 3C-F ).