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Targeting KRAS reprograms a Treg-dominant immunosuppressive microenvironment and sensitizes KRAS-mutant gastric adenocarcinoma to CTLA-4 immunotherapy

Sci China Life Sci. 2026 Sep 3. doi: 10.1007/s11427-026-3438-4. Online ahead of print.

ABSTRACT

Oncogenic KRAS mutations define a distinct molecular subset of gastric adenocarcinoma (GA), yet their impact on the tumor immune microenvironment remains incompletely understood. In this study, we established a genetically faithful and immunocompetent KRASG12D-driven mouse model of GA, together with matched organoids and cell lines, to investigate how oncogenic KRAS shapes tumor-immune interactions. KRAS-mutant tumors consistently developed an immunosuppressive microenvironment characterized by enrichment of regulatory T cells (Tregs), accompanied by reduced cytotoxic lymphocyte infiltration and intrinsic resistance to PD-1 blockade. Although pharmacologic targeting of KRAS effectively suppressed tumor growth and increased immune cell infiltration, functional immune analyses revealed persistent Treg-mediated immunosuppression that limited effective antitumor immunity. Mechanistically, TGF-Ξ² signaling was required to maintain Treg dominance and suppress effector T cell function in KRAS-driven tumors. Importantly, disruption of this suppressive axis through combined KRAS inhibition and CTLA-4 blockade attenuated TGF-Ξ² activity, impaired Treg function, and enhanced antitumor immune responses in vivo. Collectively, these findings identify oncogenic KRAS as a key regulator of TGF-Ξ²-dependent immune suppression in GA and provide mechanistic insight into immune evasion within this molecular subtype.

PMID:42714795 | DOI:10.1007/s11427-026-3438-4

Adversarial Error Correction for Visual Autoregressive Generation

arXiv:2605.24843v1 Announce Type: cross Abstract: Visual Autoregressive (VAR) models have emerged as a powerful paradigm for image synthesis by performing hierarchical next-scale prediction. However, VAR models are inherently prone to cascading error propagation, where subtle coarse-scale mispredictions are amplified across the hierarchy, ultimately distorting the final synthesis. To mitigate this, we propose AID-VAR, a plug-and-play framework that enhances pre-trained VARs through Adversarially Injected Diagnosis. Instead of a standard passive generation, AID-VAR introduces a proactive error-correction mechanism inspired by the adversarial feedback in GANs. We deploy a discriminator to diagnose fidelity gaps at each scale transition, coupled with a lightweight guidance injector. This module operates as a non-invasive adapter that refines the feature manifold of a frozen VAR backbone, effectively steering the generation toward the distribution of real images without destabilizing the pre-trained latent space. Furthermore, to rigorously evaluate this cross-scale progression, we introduce the Inter-Scale Consistency Score (ISCS), a novel metric that quantifies the fidelity and structural alignment between consecutive resolution scales. Experimental results across various backbones demonstrate that AID-VAR delivers sharper textural details and fewer structural distortions with negligible overhead. For instance, AID-VAR-d20 achieves a 16% improvement in FID with only a 3% increase in parameters. These results establish AID-VAR as a highly efficient and scalable pathway for upgrading large-scale VAR generators, enhancing global coherence and local detail without altering training data, base architectures, or sampling schedules. Code is available at https://github.com/bijiw515/AID-VAR.

How Controllable Are Large Language Models? A Unified Evaluation across Behavioral Granularities

arXiv:2603.02578v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly deployed in socially sensitive domains, yet their unpredictable behaviors, ranging from misaligned intent to inconsistent personality, pose significant risks. We introduce SteerEval, a hierarchical benchmark for evaluating LLM controllability across three domains: language features, sentiment, and personality. Each domain is structured into three specification levels: L1 (what to express), L2 (how to express), and L3 (how to instantiate), connecting high-level behavioral intent to concrete textual output. Using SteerEval, we systematically evaluate contemporary steering methods, revealing that control often degrades at finer-grained levels. Our benchmark offers a principled and interpretable framework for safe and controllable LLM behavior, serving as a foundation for future research.
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