PMC9742598_01
(A) The timeline and representative CT and MRI images. CT of March 2020, yellow arrow points toward intrahepatic lesions in S6/S8 at tumor metastasis. CT of June 2020 revealed stable disease was observed after 2 cycles of nab-paclitaxel/cisplatin plus pembrolizumab. CT of October 2020, partial remission was observed after 3 cycles of nab-paclitaxel/cisplatin plus pembrolizumab and 5 cycles of nab-paclitaxel plus pembrolizumab. CT of May 2021, continuous partial remission was observed after 10 cycles of pembrolizumab maintenance therapy. In July 2022, MRI showed durable partial remission. S6, Segment 6; S8, Segment 8; SD, stable disease; PR, partial remission. (B) Image changes during prednisolone treatment after the onset of CIP. CIP was significantly relieved, as seen in the images. The red arrow points to the part where CIP occurred. CIP, checkpoint inhibitor pneumonitis.
fphar-13-1037646-g001.jpg
PMC9742598_01_fphar-13-1037646-g001.jpg
F1
S8 (Figure 1A). The first radiological imaging in June 2020 showed a stable disease after two cycles (Figure 1A). Subsequent ten cycles of pembrolizumab monotherapy (the maintenance therapy) were administered and stopped in May 2021, when grade 2 checkpoint inhibitor pneumonitis (CIP) was observed (Figure 1B). The patient survived for over 27 months after the chemoimmunotherapy and was still in continuous remission at the last follow-up in July 2022 (Figure 1A ).
Tumor pathological findings. (A) Hematoxylin and eosin staining of the patient's tumor. Magnification, x200; (B) Multiple immunofluorescence of the TME: (a): Green for PD-1; Yellow for PD-L1; Pink for CD8; Cyan for CD68; Red for CD163. Magnification, x200. (b): Pink for CD3; Red for CD4; Green for CD20; Cyan for CD56; Yellow for FoxP3. Magnification, x200.
fphar-13-1037646-g002.jpg
PMC9742598_01_fphar-13-1037646-g002.jpg
F2
Meanwhile, laboratory examinations showed that the patient's carcinoembryonic antigen (CEA) was 7.69 ng/ml (normal level < 3.4 ng/ml), and the carbohydrate antigen 19-9 (CA 19-9) was 33.10 U/ml (normal level < 22 U/ml). Subsequently, the patient underwent next-generation sequencing (NGS) on surgically resected specimens, and the results showed KRAS and TP53 mutations, TMB of 1 mutation/megabase, and MSS. Multiple immunofluorescence was used to detect TME (Figure 2), indicating that PD-L1 expression was negative (TPS< 1%, CPS< 1) and CD8+ TIL expression was quantified at 0.21% of the tumor parenchyma and 1.15% of the stroma (Table 1).
PET-CT in August 2020 showed disappeared hypermetabolic activities in the hepatic lesions and no clear sign of tumor recurrence and metastasis throughout the body. S6, Segment 6; S8, Segment 8.
fphar-13-1037646-g003.jpg
PMC9742598_01_fphar-13-1037646-g003.jpg
F3
The response of tumor marker to chemoimmunotherapy. CA19-9, carbohydrate antigen 19-9.
fphar-13-1037646-g004.jpg
PMC9742598_01_fphar-13-1037646-g004.jpg
F4
The patient's CEA and CA 19-9 levels also returned to the normal range (Figure 4). The most common adverse events were hematologic toxicities (grade 2 leukopenia, grade 2 neutropenia and grade 1 anemia) during chemoimmunotherapy.