Cancer Cell最新文献

The diversity of tumor-associated macrophages presents a major challenge to the clinical translation of myeloid cell-targeting strategies. In this issue of Cancer Cell, Yagel et al. and Mateus-Tique et al. demonstrate that IL-12 armored CAR T cells effectively target tumor-promoting macrophage populations and reset the microenvironment toward an anti-cancer mode.

Molecular mechanisms underlying sex-specific differences in cancer incidence and therapy responses are under intense investigation. Here, we report sex-biased functions of Yap1 in multiple cancer types in human and mouse. Through integrated multi-omics analyses, we demonstrate that Yap1 deletion significantly extends survival in male but not female Sonic Hedgehog (SHH) medulloblastomas (MB) models. While Yap1 is required to maintain stem-like cells in both sexes, Yap1 plays a more critical role in immune evasion in males. Mechanistically, YAP1 is essential for activating Cd276/B7-H3 expression to mediate CD8⁺ T cell suppression in males. Consistently, CD276 inhibition extends survival in male but not female SHH MB. Moreover, in vivo targets of YAP1 stratify survival in male but not female patients with medulloblastoma, glioblastoma, mesothelioma, and lung cancer. This study provides evidence for sex-biased functions of Yap1 and CD276 in MB immune suppression and highlights the importance of biological sex in cancer:immune interactions.

Recent controversy in the cancer microbiome field highlights the need for more reliable microbial detection from human genomic data. Here, we develop PRISM, an efficient computational framework for precise microorganism identification and decontamination from low-biomass sequencing data. PRISM achieves robust performance when benchmarked on 230 independent datasets with known true-positive and contaminant taxa. We then use PRISM to profile 25 cancer types from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium. We identify consistent microbial signatures in gastrointestinal tract, head-and-neck, and urogenital tract tumors, and sparse signal elsewhere. In pancreatic cancer, we associate microbial detection with altered host protein glycosylation pathways and greater smoking exposure. Lastly, we consider the impact of sequencing approaches on positive and negative data interpretation. Overall, PRISM improves the reliability of microbial profiling and allows leveraging of existing human genomic data for the concurrent detection of host-microbial signatures with potential molecular and clinical significance.

Tumor-associated neutrophils (TANs) are abundant across cancers, yet their phenotypic diversity and functional states remain poorly defined. Here, we introduce a cell-type probability classifier that recovers low-transcript neutrophils from scRNAseq datasets, enabling pan-cancer analyses of TAN heterogeneity. Across >190 human and murine tumors, we identify a conserved differentiation trajectory that culminates in a terminal CCL3^hi state. This state exhibits pro-tumor transcriptional programs, including those involved in hypoxic adaptation and senescence. Consistently, CCL3^hi TANs are enriched in hypoxic tumor niches in both humans and mice. Through mechanistic perturbations of neutrophil-derived CCL3 in mice, we show that it sustains TAN survival in hypoxic tumor regions via CCR1-dependent signaling. These findings establish CCL3 as a conserved marker and functional driver of pro-tumor neutrophils in growing tumors, and provide a scalable framework for dissecting neutrophil biology across cancer types.