In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Purpose: To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU). Materials and Methods: A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models. Results: Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p<0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p>0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p<0.001). Conclusion Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

An adult castrated male dog was presented with persistent hematochezia. Digital rectal examination and endoscopy found multiple colorectal masses. Complete blood count and serum biochemical results were within the reference interval. Fine needle aspirate of the masses indicated a diagnosis of inflamed polyps with a primary differential of malignancy. Histopathologic examination using endoscopy-guided incisional biopsy of the masses revealed an inflamed neoplasm with ossification. A colectomy was performed to remove the tumor. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of colorectal carcinoma in situ (CiS) with immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. The immunohistochemistry confirmed intraepithelial CD3 + T cells within CiS. The flow cytometric analysis indicated tumor-infiltrating CD4 + T, CD8 + T, and CD11b + myeloid subsets. The flow cytometric analysis of circulating and tumor-infiltrating leukocytes demonstrated a preferential expansion of CD25 + FOXP3 + regulatory T cells within CiS. To the author’s knowledge, this is the first report to show clinical evidence emphasizing the immunogenicity and immune-suppressive environment of canine colorectal CiS. Our case will be valuable in providing a rationale for basic research that dissects the immune environment for canine colorectal cancers for the future development of cancer immunotherapy.

An adult female dog was presented for evaluation of rapid growth of mammary gland masses. Complete blood count, serum biochemistry, and diagnostic imaging results were unremarkable. Fine needle aspirates of the mammary masses indicated mammary carcinoma characterized by large globoid cells with finely granular eosinophilic globules or Melamed-Wolinska-like bodies. A regional mastectomy was performed on the masses. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of mammary comedocarcinoma with nodal metastasis and distinct perivascular immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. Immunohistochemical examination confirmed the infiltration of CD3 + T and PAX5 + B lymphocytes. Flow cytometric analysis demonstrated tumor-infiltrating CD4 + CD25 + FOXP3 + regulatory T, CD8 + T, CD11b + myeloid, and CD21 + B cells. Of note, paired flow cytometric analysis of peripheral blood and tumor tissues showed a preferential tumor infiltration of regulatory T and B cells. Approximately two months after the mastectomy, the tumor reoccurred at the surgery site. The dog died due to deteriorating conditions. We report a rare case of canine mammary comedocarcinoma, providing clinical, clinicopathologic, histologic, and immunophenotypic characteristics. Our case is valuable in providing a rationale for basic research that maps the immune landscape of mammary comedocarcinoma to identify key immune subsets for cancer progression.

Background: This study evaluated the prevalence of Helicobacter pylori infection and the risk factors associated with H. pylori transmission among spouses. Methods: We assessed the spousal concurrence of H. pylori infection using the Campylobacter-like organism (CLO) test under gastro-endoscopy in 132 couples. Based on the CLO test results, participants were categorized into H. pylori concurrent and independent groups. The chi-square test and Student t-test were performed for demographic comparisons between the concurrent and independent H. pylori groups. In addition, multivariate logistic regression analysis was performed to identify factors associated with concurrent H. pylori infection. Results: The study revealed that the concurrence rate of H. pylori infection was 42.4% in married Korean couples. The odds ratio (OR) derived from the concurrence of H. pylori infection tended to decrease in older couples (OR, 0.975; 95% confidence interval [CI], 0.949–1.002; P=0.072). Gastric erosion was also associated with a decreased OR for concurrent infection (OR, 0.488; 95% CI, 0.295–0.808; P=0.005). Conversely, active duodenal ulcers were associated with an increased OR for concurrent infections (OR, 6.501; 95% CI, 1.267–33.346; P=0.025). Duodenal ulcer scars tended to increase the OR of concurrent infections (OR, 1.392; 95% CI, 0.815–2.380; P=0.226). Conclusion Spousal transmission and concurrence of H. pylori infection were negatively associated with gastric erosion; however, they were positively associated with active duodenal ulcers. Further studies are warranted to elucidate the mechanisms underlying these findings.