Wei Peng

Immunotherapies achieve durable responses in several cancers but show limited efficacy in refractory hepatocellular carcinoma (HCC). The mechanisms by which hepatoma cells evade immune recognition and limit immune checkpoint blockade (ICB) efficacy are incompletely defined. Here, we identified tumor-intrinsic tescalcin (TESC) as a previously unrecognized phagocytic checkpoint that contributes to immune evasion and ICB resistance in HCC. Mechanistically, H3K4 methylation drove TESC expression in hepatoma cells, facilitating cytosolic Ca ²⁺ buffering and attenuating endoplasmic reticulum (ER) stress–induced calreticulin (CALR) plasma membrane exposure, an essential “eat-me” signal. Consequently, this process abrogated membrane CALR-directed phagocytosis by antigen-presenting cells (APCs), including macrophages and DCs, thereby impairing antigen presentation and subsequent T cell activation. Clinically, we found that elevated H3K4me3-TESC signaling was a promising prognostic biomarker for a poor ICB response in HCC. Importantly, in vivo disruption of this axis restored APC phagocytic function and enhanced the antitumor effects of ICB therapy. Therefore, targeting TESC-driven immune escape and its underlying epigenetic regulation may restore APC function and offer a precise therapeutic strategy to enhance immunotherapeutic efficacy in HCC.

Background: The ipsilateral renal parenchymal volume (RPV) experiences a sharp decrease shortly after partial nephrectomy (PN), mainly due to surgical remove or devascularization of kidney tissue. However, the subsequent change of RPV and its association with glomerular filtration rate (GFR) fast decline remains unknown. Our objective was to investigate the change of ipsilateral RPV and renal function status from new baseline (1–12 months after PN) to latest follow-up (≥1 year) after PN, and to explore factors associated with ipsilateral RPV decrease rate and correlation between RPV decrease and GFR fast decline. Materials and methods: A retrospective review of 367 patients with PN was conducted. Three-dimensional reconstruction of computed tomography (CT)/MRI images was performed for RPV calculation. Spectrum score was used to assess the degree of acute kidney injury (AKI) in the operated kidney after PN. GFR decline greater than 3 ml/min/1.73 m²/year was defined as GFR fast decline. One hundred fourteen patients underwent abdominal surgery was used as control. Predictive factors for subsequent decrease of RPV rate and GFR fast decline were evaluated by linear and logistic regression, respectively. Results: With a median interval time of 21.1 (interquartile range:13.8–35.5) months, median ipsilateral RPV significantly decreased from 118.7 (interquartile range:100.7–137.1) ml at new baseline to 111.8 (IQR: 92.3–131.3) ml at latest follow-up. The interval time [β: 1.36(0.71–2.01), PPP=0.03] and overweight [odds ratio:1.63 (1.02–2.60), P=0.04] were independent predictors of GFR fast decline. Conclusions: Ipsilateral RPV experienced a moderate but significant decrease during follow-up after PN, especially in those with severer acute kidney injury. The presence of GFR fast decline was found to be associated with reduction of ipsilateral RPV, particularly in overweight individuals.