Biology subjects

Procell, L.

Publications and source records attributed to Procell, L..

3 recordsLinked to original sources

bioRxiv2026

Cancer cell adaptations along a proliferation-robustness axis drive TME pro-tumor phenotypes

Tumors are highly complex dynamic ecosystems with causal relationships between cancer cells and their tumor microenvironment (TME). To disentangle these interactions, we performed long-term co-culture experiments with cancer cells evolving alongside continuously replenished fibroblasts or macrophages. This allowed us to distinguish between adaptive and physiological responses in specific cancer-TME interactions, which we then also recapitulated in patient tumors. We found that co-culture with fibroblasts induced the epithelial-mesenchymal transition in cancer cells and resulted in their increased drug tolerance, while co-culture with macrophages promoted stress, hypoxia responses and enhanced tumorigenicity. Adaptations were recurrent and partially reversible, but could not be explained by clonal selection, suggesting a dynamic non-mutational process. Moreover, adapted cancer cells elicited cell state changes in the fibroblasts and macrophages consistent with an extended phenotype mode of cancer evolution. Our findings reframe cancer-TME interactions by a systematic dissection according to sets of specific adaptations and programmed responses.

cancer biology↗

bioRxiv2026

Rethinking the Benign Nature of Class II Lupus Nephritis

Introduction: Class II lupus nephritis (LN) is considered clinically benign, yet up to 50% of patients progress to more severe disease and no molecular characterization exists. We aimed to define the single-cell landscape of Class II LN and identify cellular and transcriptional features associated with kidney outcome. Methods: We performed single-cell RNA sequencing on kidney biopsies from fifteen Class II LN patients (eight de novo, seven regressed from prior proliferative or membranous disease) and six healthy controls, integrated with 155 LN and 30 healthy-control samples from the Accelerating Medicines Partnership in SLE spanning proliferative, membranous, and mixed LN. Findings were correlated with 52-week renal response and supported by urinary proteomics. Results: Despite histologically minimal changes, Class II LN exhibited marked immune cell expansion comparable to proliferative and membranous LN, including CCL3+ CCL4+ intermediate monocytes producing TNF, FOLR2+ SIGLEC1+ macrophages producing TGF{beta} and PDGF, and CD69+ CD8+ effector memory T cells producing IFN{gamma}. Fibroblasts and myofibroblasts were significantly expanded and displayed divergent transcriptional programs: pro-fibrotic and inflammatory myofibroblast modules were associated with worse 52-week outcomes, while interferon-responsive and matrix-remodeling fibroblast programs were associated with improvement. Pathogenic and protective fibroblast populations received overlapping immune-derived signals, suggesting that fibroblast transcriptional state, rather than the identity of incoming signals, shapes the stromal response. Baseline chronicity index captured this stromal heterogeneity and was the clinical parameter most associated with outcome. Urinary proteomics aligned Class II with proliferative rather than membranous disease. Conclusions: Class II LN harbors substantial molecular activity not captured by routine histology. Fibroblast transcriptional programs and baseline chronicity index are candidate correlates of kidney outcome that warrant validation in larger, prospectively followed cohorts.

genomics↗

bioRxiv2025

Multiomic characterization, early detection, and therapeutic targeting of myeloid sarcoma

Myeloid sarcoma, an aggressive extramedullary subtype of acute myeloid leukemia (AML), occurs in [~]10% of patients, and has not yet been included in large-scale genomic studies. The critical biological changes that drive tumor evolution are unknown, its detection in asymptomatic patients remains a clinical challenge, and treatment options are limited as patients are often excluded from clinical trials, rendering it a neglected disease entity. Based on comprehensive multi-omic profiling, we demonstrate that myeloid sarcoma evolves from medullary AML with distinct sitespecific clonal evolution patterns. Additionally, we show that circulating tumor DNA sequencing can serve as a non-invasive method for molecular profiling of myeloid sarcoma, offering a novel avenue in molecular diagnostics. We characterize unique transcriptional profiles of myeloid sarcoma, reflecting immune evasion and adaptation to an extramedullary microenvironment. We provide evidence for a key role of RAS pathway activation and demonstrate in murine models of myeloid sarcoma that RAS inhibition effectively reduces tumor burden. Overall, our data highlight key differences between medullary AML and myeloid sarcoma including universal molecular evolution and RAS pathway activation as hallmarks of the disease and nominate RAS inhibition as a promising therapeutic strategy for patients with myeloid sarcoma.

cancer biology↗