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Accelerating Long-Tail Generation in Synchronous RLHF Training via Adaptive Tensor Parallelism

arXiv:2605.23945v1 Announce Type: new Abstract: Reinforcement Learning from Human Feedback (RLHF) has become a key post-training paradigm for improving model quality. However, the synchronous three-stage RLHF pipeline is often bottlenecked by the generation stage, where response-length skew causes the effective batch size to shrink rapidly during decoding, leaving GPUs underutilized while a few long responses remain unfinished. Mainstream frameworks employ a static tensor parallelism (TP) configuration that cannot adapt to changing batch characteristics, leaving substantial performance headroom unexplored. We propose PAT, an adaptive TP method that dynamically reconfigures TP during the generation stage of each RLHF iteration. PAT introduces two key techniques. First, a predictor-guided online reconfiguration method decides both the reconfiguration point and the target TP configuration based on offline profiling, triggering reconfiguration only when the predicted latency benefit outweighs the reconfiguration overhead. Second, a lightweight online reconfiguration mechanism updates only the states and layouts affected by TP changes: it adapts unfinished decoding states through a cost-model-based choice between KV-cache migration and recomputation, performs in-place weight resharding, and reuses cached communication groups. We implement PAT on top of SGLang and integrate it with the VeRL framework. Evaluations on LLaMA3.1-8B and Qwen3-14B using DeepScaleR show that PAT reduces generation latency by up to 34.6% and end-to-end RLHF training iteration latency by up to 27.2% compared to the original VeRL setup.

CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8+ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8+ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8+ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8+ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1+ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8+ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8+ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8+ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8+ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1+ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

CR1(+) tumor-associated macrophages orchestrate an immunosuppressive niche in hepatocellular carcinoma: a genetic and multi-omics dissection

J Transl Med. 2026 May 25. doi: 10.1186/s12967-026-08301-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden and a leading cause of cancer-related mortality. Advanced disease is characterized by a profoundly immunosuppressive tumor microenvironment (TME) and limited durable responses to therapy. However, the upstream genetic determinants that drive tumor-associated macrophage (TAM) dysfunction in HCC remain poorly defined. Using an integrative genetic and multi-omics framework, we investigated complement receptor 1 (CR1) as a candidate regulator of this immunosuppressive niche.

METHODS: We combined Mendelian randomization (MR) and metabolite mediation analyses with bulk, single-cell, and spatial transcriptomics to define the role of CR1 in HCC. Public datasets included the TCGA-HCC cohort, a single-cell RNA-sequencing dataset comprising 53,474 high-quality cells from 21 samples, and two spatially profiled HCC sections. Clinical validation was performed in 30 paired HCC and adjacent liver tissues. Functional assays were conducted in THP-1-derived macrophages using CR1 gain- and loss-of-function approaches, phagocytosis assays, and macrophage-CD8+ T-cell co-culture experiments.

RESULTS: MR analyses implicated CR1 in HCC susceptibility at both the protein and transcript levels. pQTL analysis linked genetically predicted circulating CR1 levels to HCC risk (IVW OR = 1.403, p = 0.017), and mediation analysis identified specific metabolites as candidate intermediates. Integrative multi-omics analyses showed that CR1 was preferentially enriched in TAMs, spatially co-localized with the M2 marker CD206, and associated with reduced CD8+ T-cell infiltration, enhanced T-cell exhaustion signatures, advanced clinicopathological features, and poorer survival. In 30 paired clinical samples, CR1-high tumors exhibited increased M2-like macrophage accumulation and reduced CD8+ T-cell infiltration. Functionally, CR1 overexpression drove macrophages toward an M2-like phenotype, enhanced phagocytic activity, increased PD-L1 expression, and suppressed CD8+ T-cell proliferation as well as IFN-gamma and granzyme B production, whereas CR1 knockdown produced the opposite phenotype.

CONCLUSIONS: Our study provides the first integrated genetic, spatial, and functional evidence that CR1+ TAMs constitute a clinically relevant immunoregulatory axis in HCC. These findings extend current understanding of complement-associated immunosuppression beyond canonical complement cascade activity and support CR1 as a candidate biomarker and therapeutic target for macrophage reprogramming, with potential translational relevance for combination strategies involving immune checkpoint blockade.

PMID:42185899 | DOI:10.1186/s12967-026-08301-z

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