Weijiao Du's research while affiliated with Tianjin Medical University Cancer Institute and Hospital and other places

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T‐cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4 ⁺ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8 ⁺ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the G T score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed G T score can reflect the prognosis of patients with stage III LUAD more effectively than T‐cell density. The exploration of the T‐cell spatial landscape may suggest potential cell–cell interactions and therapeutic targets and better guide clinical decision‐making. © 2024 The Pathological Society of Great Britain and Ireland.

This study aimed to examine the spatial distribution of immune cells by application of Gcross function in 170 patients with stage I-IIIA lung adenocarcinoma (LUAD) and explore its prognostic value. A total of 170 stage I-IIIA LUAD patients who underwent radical surgery were enrolled. Paraffinized tumor sections were collected for two panels of multicolor immunofluorescence staining as follows: Panel 1 (CD4, CD8, FOXP3, CD69, CD39, CD73, and DAPI) and Panel 2 (CD68, CD163, CD20, CD11c, PDL1, IDO, and DAPI). The immune cells were categorized as CD8+, CD4+ T-helper cell (CD4Th), Regulatory T cell (Treg), Macrophage type 1 (M1), Macrophage type 2 (M2), Dendritic cell (DC) and B cell. The immune cell numbers were enumerated, and the immune cell proximity score was calculated employing the Gcross function. The correlation between immune cell variables and Disease-Free Survival (DFS) was explored through univariate Cox regression analyses. Factors with P<0.05 were subjected to multivariate analyses. According to univariate Cox regression analyses, total PDL1+ and PDL1+ DC counts were negative factors (P=0.003, 0.031). CD4Th and IDO-DC counts were positive factors (P=0.022, 0.024). The proximity score (M1 to M2) was a positive factor for DFS (P=0.032), and the proximity score (PDL1+DC to M1) was a negative factor (P=0.009) according to univariate Cox analyses. In multivariate analyses, stage (IIIA vs. I+II) [HR: 1.77(1.18, 2.64), P=0.006] and proximity score (PDL1+DC to M1) [HR: 1.60(1.07, 2.37), P=0.021] were independent negative factors and CD4Th counts [HR: 0.60(0.40, 0.90), P=0.013] was an independent positive factor. Our study indicated that a higher level of tumor-infiltrating CD4Th cells predicted longer DFS, and a closer proximity of PDL1+ DCs to M1 cells was associated with dismal DFS in stage I-IIIA LUAD patients.

ECD is considered to have rapid progression and poor prognosis. Studies have shown that vemurafenib is effective for ECD patients with orbital involvement, but not for ECD with multiple organs. The refinement of treatment approaches and the increased awareness of ECD have led to a dramatic improvement in prognosis.

Background: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with unique features at histological and molecular levels. The prevalence of OCCC is higher in east Asia than in Western countries. As cases are usually chemo-resistant, treatment effects of platinum-based chemotherapy are not satisfactory, especially for patients with stage III or IV disease. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with advanced-stage cancers. However, whether advanced OCCC patients benefit from ICIs remains elusive. Case description: Herein, we report a Chinese patient with stage IIIB inoperable OCCC who was resistant to platinum-based chemotherapy and anlotinib. Next-generation sequencing (NGS) revealed a pathogenic polymerase epsilon (POLE) P286R mutation and a high level of tumor mutation burden (TMB) in tissue and plasma samples. The ICI sintilimab was then used with bevacizumab as third-line treatment. Tumor reduction was observed, and the patient underwent surgical resection which indicated a pathologic complete response (pCR). Maintenance therapy with sintilimab and bevacizumab was applied, and the patient has achieved overall survival (OS) of 35 months since the diagnosis. They have also achieved a progression-free survival (PFS) of 29 months since commencing ICI treatment and have been disease-free for 24 months after surgical resection. Conclusions: The treatment effect of ICI in POLE-mutant OCCC patients has been rarely reported. The treatment benefits observed in the stage IIIB OCCC patient who was resistant to platinum-based chemotherapy may be associated with the presence of POLE mutation and a high level of TMB. Comprehensive genomic profiling could contribute to appropriate treatment decisions for OCCC.

Introduction: Can the Cytokine-induced killer (CIK) cells in combination with immune checkpoint inhibitor further improve the efficacy of chemotherapy in non-small cell lung cancer (NSCLC) patients? What are the adverse reactions of this combination therapy? But these problems are not clear. Therefore, we conducted a phase 1b trial to evaluate the safety and efficacy of autologous CIK cells therapy combined with Sintilimab, antibody against programmed cell death-1, plus chemotherapy in untreated, advanced NSCLC patients. Methods: Patients with stage IIIB/IIIC/IV NSCLC received Sintilimab, platinum-based doublet chemotherapy, and CIK cells every 3 weeks for 4 cycles, then maintenance treatment with Sintilimab in squamous and with Sintilimab plus pemetrexed in non-squamous NSCLC until disease progression or unacceptable toxicity or two years. The primary endpoints were safety and objective response rate (ORR). Results: 34 patients received the treatment. 94.1% of patients experienced treatment-related adverse events (TRAEs). Grade 3 or greater TRAEs occurred in 64.7% of patients. One (2.9%) patient died of grade 5 immune-related pneumonia. The ORR and DCR were 82.4% (95% CI, 65.5%-93.2%) and 100.0% (95% CI, 89.7%-100.0%), respectively. Objective responses were evaluated in 14 of 15 non-squamous patients (93.3%; 95% CI, 68.1%-99.8%) and in 14 of 19 squamous patients (73.7%; 95% CI, 48.8%-90.9%). Median PFS was 19.3 months (95% CI, 8.3 months to not available). Conclusion: Autologous CIK cells immunotherapy in combination with Sintilimab plus chemotherapy was well tolerable and showed encouraging efficacy in patients with previously untreated, advanced NSCLC (ClinicalTrials.gov number, NCT03987867).

Objective: Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs. Methods: From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests. Results: At the onset of AEs in the irAE group, ferritin (normal range, 35-150 μg/L) rose to a median of 927 μg/L (range, 117-17,825 μg/L) from 86 μg/L at baseline (range, 29-421 μg/L) (P < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 μg/L; range, 32-478 μg/L) (P < 0.001) and the AE group (median, 103 μg/L; range, 23-712 μg/L) (P < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died. Conclusions: Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non‐small cell lung cancer (NSCLC) with an extremely poor prognosis making it a therapeutic challenge. However, the development of genetic variation molecular diagnosis and targeted agents has brought the treatment of such malignancies to the precision era. Co‐existing mutations of EGFR and MET have been reported in NSCLC, but rarely found in PSC. We herein present a rare case of a 74‐year‐old female patient diagnosed with PSC, carrying an activating mutation in exon 21 L858R of EGFR and a concurrent MET amplification prior to treatment. Combined application of gefitinib and crizotinib, inhibitors targeting EGFR and MET, respectively, was prescribed. The patient experienced a partial response and was stable for 9.7 months off therapy. The observation stresses the importance of genetic testing and paves the way for combined targeted strategies in PSC. PSC patients harboring both EGFR mutation and MET amplification may benefit from combined EGFR and MET inhibitors. The combination of these two drugs in PSC is rarely reported some more large‐scale clinical trials are required to confirm this result.

Pulmonary sarcomatoid carcinoma; non-small cell lung cancer; EGFR mutation; MET amplification; crizotinib/gefitinib