PMC9606775_01
Representative images of CT scans for lesions. (A) CT scans showed changes in primary and metastatic lesions after combination therapy. C2-C10 represents the re-examination every two cycles, P represents the primary lesions, and M1-M7 represents the 7 liver metastases. (B) The histogram demonstrated the change trends in primary tumor and liver metastases, including maximum tumor diameter (Y-axis) corresponding to the treatment timeline. The X-axis shows the treatment circle.
fimmu-13-1016647-g001.jpg
PMC9606775_01_fimmu-13-1016647-g001.jpg
f1
Abdominal enhanced computed tomography (CT) scan showed space-occupying lesions in the neck of the pancreas, multiple enlarged lymph nodes around the pancreas and retroperitoneum, accompanied by multiple space-occupying lesions in the right lobe of the liver, considered to be pancreatic cancer with liver metastases ( Figure 1A ). CT scan examination pictured the patient's primary lesions were dramatically shrinking, compared to the last CT-scan results, ( Figure 1A ), however, there was little change in liver metastases during the first two cycles of treatment. Continuing treatment, the patient's primary lesions, and liver metastases continue to shrink over the same period. Surprisingly, after 1 cycle of new treatment regimens as mFOLFIRINOX, CT scans illustrated that the primary lesion was significantly smaller than in the previous cycle, and the liver metastases were decreasing ( Figure 1A ). Histograms show trends in primary tumors and liver metastases and exact values for each stage ( Figure 1B ).
Pathological examination results. (A) The hematoxylin-eosin (H&E) staining in the microscopic observation (400x). (B) IHC of liver metastases of pancreatic ductal adenocarcinoma showed CK8/18+, Syn-, CDX-2-, CK7+, CK20-, Hepatocyte-, Glypican-3-, C-erB-2(0), Ki67 (60%+), original magnification x400. (C) PD-L1 IHC staining of hepatic metastases tested that the Tumor cell Proportion Score (TPS) is 2-4, and the Combined Positive Score (CPS) is 2-4.
fimmu-13-1016647-g002.jpg
PMC9606775_01_fimmu-13-1016647-g002.jpg
f2
Later a liver biopsy was confirmed to be a moderately to poorly differentiated adenocarcinoma ( Figure 2A ). Immunohistochemical (IHC) results showed CK8/18+, Syn-, CDX-2-, CK7+, CK20-, Hepatocyte-, Glypican-3-, C-erB-2(0), Ki67 (60%+), ( Figure 2B ) and serum tumor markers test were abnormal, carbohydrate antigen 125 (CA125): 41.9U/ml, carbohydrate antigen 19-9 (CA199) >1000U/ml ( Figure 3A ). Figure 2C ). This patient's primary diagnosis was pancreatic ductal adenocarcinoma with liver metastasis and thrombus in right lower extremity. Furthermore, the patient's Tumor-Node-Metastasis (TNM) stage, cT3N1M1, Karnofsky score, 80 points, Eastern Cooperative Oncology Group (ECOG) score, 1 point, visual analogue scale (VAS) score,6 points, and nutrition risk screening (NRS), 3 points.
Laboratory examination results during the clinical course. (A) Trends in the level of tumor markers, including CA 199, CA125, and CEA (right Y-axis) correspond to the treatment timeline. (B) Trends in the level of weight changes corresponding to the treatment timeline. (C). Trends in the level of blood routine examination, including PLT, HBC, and WBC (right Y-axis) correspond to the treatment timeline. (D) Trends in the level of biochemical indicators, including ALT, AST, and Bilirubin (right Y-axis) correspond to the treatment timeline. All X-axes show the date of disease progression. (CEA, carcinoembryonic antigen; CA199, carbohydrate antigen 19-9; CA125, carbohydrate antigen 125, WBC, white blood cell count; HBC, hemoglobin; PLT, blood platelet count, ALT, alanine aminotransferase; AST, aspartate aminotransferase).
fimmu-13-1016647-g003.jpg
PMC9606775_01_fimmu-13-1016647-g003.jpg
f3
Immunohistochemical (IHC) results showed CK8/18+, Syn-, CDX-2-, CK7+, CK20-, Hepatocyte-, Glypican-3-, C-erB-2(0), Ki67 (60%+), ( Figure 2B ) and serum tumor markers test were abnormal, carbohydrate antigen 125 (CA125): 41.9U/ml, carbohydrate antigen 19-9 (CA199) >1000U/ml ( Figure 3A ). However, after 9 cycles of treatment, the patient's tumor markers CA-199 doubled from its previous nadir ( Figure 3A ) and the primary lesion has grown larger than the previous one. The patient's liver function impairment, thyroid function, and pancreatic function were basically normal ( Figure 3D ). The most serious treatment-related adverse events (TRAEs) of this patient throughout the clinical course were grade 2 leukocytopenia and grade 2 anemia, which was recovered under drug intervention before the next cycle of treatment ( Figure 3C ). Up to now, the patient's weight has remained basically stable ( Figure 3B ).
Flow cytometry results. Findings showed the number of PD1+CD8 positive cells was 212/10,000; The proportion of CD3-CD19-CD14+CD16-HLA-DR positive cells was 65.36%, and all the above cell numbers were positive.
fimmu-13-1016647-g004.jpg
PMC9606775_01_fimmu-13-1016647-g004.jpg
f4
The immune checkpoint expression test report showed that the number of PD1+CD8 positive cells was 212/10,000; The proportion of CD3-CD19-CD14+CD16-HLA-DR positive cells was 65.36%, detected by a peripheral blood cell flow cytometer ( Figure 4 ).