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Global Translational Medicine                                                 SLE patient underwent PD



            therapy with tacrolimus (2 mg BID) and mycophenolate   the patient experienced nausea, vomiting, weight loss,
            mofetil (750  mg BID) was resumed on post-operative   neutropenia, and thrombocytopenia. After two cycles of
            day 3. The post-operative course was uneventful, and the   AG chemotherapy, a CT scan showed stable disease, with
            patient was discharged after the 12   post-operative day   the liver metastasis reduced to 16 mm × 15 mm. The last
                                         th
            (Tables  1 and  2). Post-operative pathology confirmed   follow-up was in April 2024, during which the patient was
            pancreatic  adenocarcinoma  with  three  positive  lymph   still receiving AG chemotherapy.
            nodes (pT2N1). Next-generation sequencing of the     For the  silico analysis conducted to evaluate changes
            primary tumor identified five somatic mutations (TP53   in the immune microenvironment, we first obtained
            c.711G>A,  KRAS c.35G>T,  ALK c.903G>T,  SMAD4     transcriptomic data of tumor tissues from pancreatic
            c.296G>T, and  NCOA3 c3820_3828delCAGCAGCAA).      cancer patients in the PACA-AU dataset  (The International
                                                                                              9
            The tumor mutation burden was low (4.8/megabase), and   Cancer Genome Consortium, https://dcc.icgc.org/) and
            microsatellite instability was not detected. The patient   The Cancer Genome Atlas (TCGA) dataset  (downloaded
                                                                                                 10
            achieved a complete tumor resection with a negative margin   through UCSC Xena browser, https://xenabrowser.net/
            (R0). Considering his history of renal transplantation,   datapages/). Expression data from the gene expression
            the patient was deemed unlikely to tolerate the modified   omnibus (GEO) database (GSE103787 ) was used to
                                                                                               11
            FOLFIRINOX regimen. Therefore, adjuvant chemotherapy   compare the immune cell infiltration ratios in lymph nodes.
            with tegafur was initiated after a 1-month follow-up. By   To gain a more comprehensive view of the patient’s tumor
            April 2023, serum levels of CA19-9 and CEA had decreased   microenvironment, we applied the CIBERSORT algorithm
            to normal (6.73 U/mL and 3.85  ng/mL, respectively).
            However, in January 2024, a CT scan revealed a single   (https://cibersort.stanford.edu) to extract immune cell
            liver metastasis measuring 20 mm×17 mm. Consequently,   abundance data from bulk RNA sequencing results of tumor
                                                                                 12
            the chemotherapy regimen was adjusted to nab-paclitaxel   tissue and lymph nodes.  This analysis utilized our RNA-seq
            plus gemcitabine (AG). During AG chemotherapy,     gene expression normalized values and transcriptomic data
                                                               from  public  databases  (TCGA,  PACA-AU,  and  GEO)  as
                                                               input.  Our analysis revealed that the profile of infiltrated
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            Table 1. Laboratory data
                                                               immune cells in this patient’s tumor tissue closely
            Parameter      Pre-  Post-surgery  Post-surgery   Units  resembled those found in pancreatic cancer patients within
                          surgery  11 days)  (4 months)        TCGA and PACA-AU datasets (Figure 3A and B). Notably,
            Red blood cell  8.2     3.81      4.73    10 /L    the ratios of naïve B cells, CD8  T cells, CD4  memory-
                                                                                                    +
                                                                                         +
                                                       12
            Hemoglobin         144           111           142   g/L  activated T  cells,  and  monocytes  in  this patient’s  tumor
                                                       9
            White blood cell  8.2   9.06      5.96    10 /L    tissue were higher than in most patients in the TCGA
                                                       9
            Monocytes      0.84     0.83      0.49    10 /L    and PACA-AU datasets (exceeding the mean + standard
            Platelet           370           508           235   10 /L  error value for each cell type). In addition, the patient
                                                       9
                                                               exhibited higher proportions of naïve B cells, memory B
            Albumin        42.9     41.7      41.8    g/L      cells, CD4  memory-activated T cells, regulatory T cells,
                                                                       +
            Globulin       29.1     28.7      27.2    g/L      resting natural killer cells, and activated dendritic cells in
            Serum creatinine       71  82.4   75.6   μmol/L    the lymph nodes compared to patients in the GSE103787
            Serum urea         3.6           3.3           2.6  μmol/L  dataset (exceeding the mean + standard error value for
            CA19-9             99           -  7.21   U/mL     each cell type) (Figure  3C). To estimate the immune
            Carcinoembryonic   6.71           -  3.88   U/mL   status of this patient, we further compared the expression
            antigen                                            of  cytotoxic  genes  –  such  as  granzyme  B  (GZMB),  IL2,
            Abbreviation: CA19-9: Carbohydrate antigen 19-9.   interferon-gamma,  IL12B,  IL4,  IL10,  IL12A, perforin 1
                                                               (PRF1), lysosomal associated membrane protein 1, and
            Table 2. Timeline of the case report               tumor necrosis factor – in the tumor tissue and lymph
                                                               node of this patient with those in the TCGA, PACA-AU,
            Date                       Information             and GSE103787 datasets. We found that the GZMB and
            December 8, 2022  Patient referred to our hospital  PiRF1 expression levels in this patient were higher than
            December 9 – 10, 2022  Pre-operative examination   those observed in the TCGA, PACA-AU, and GSE103787
            December 9, 2022  Percutaneous transhepatic cholecystostomy  datasets (higher than the value of mean + standard error)
            December 14, 2022  Pancreaticoduodenectomy         (Figure 3D-F). This finding suggests that this patient may
                                                               have enhanced T-cell cytotoxic function and anti-tumor
            December 14–26, 2022  Post-operative observation   immunity. Immunochemistry was also performed to detect
            February 7, 2023  Chemotherapy: Tegafur, 80 mg QD  GZMB and PRF1 expression in tumor tissues (Figure 4A),


            Volume 3 Issue 3 (2024)                         3                               doi: 10.36922/gtm.2893
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