Tumor Progression from a Fibroblast Activation Protein Perspective: Novel Diagnostic and Therapeutic Scenarios for Colorectal Cancer

Rossetti, Martina; Stanca, Stefano; Del Frate, Rossella; Bartoli, Francesco; Marciano, Andrea; Esposito, Enrica; Fantoni, Alessandra; Erba, Anna Paola; Lippolis, Piero Vincenzo; Faviana, Pinuccia

doi:10.3390/diagnostics13203199

Cited by 2 publications

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy

Peng,

Janićijević,

Loureiro

et al. 2024

Preprint

View full text Add to dashboard Cite

The efficiency of immunotherapy stays limited for solid tumors. It is mainly caused by the tumoral structural heterogeneity and its complex microenvironment, which impede the infiltration of immune cells into malignant tissues. Mimicking this environment in frames of microphysiological models remains a challenge, significantly increasing costs of the clinical translation for the new therapies. Here, we study a 3D multi-spheroid model incorporating prostate stem cell antigen (PSCA) modified PC3 human prostate cancer cells and fibroblast activation protein (FAP) expressing fibrosarcoma HT1080 cells embedded within the soft hydrogel microbeads. We use this model to trial the immunotherapy based on the universal chimeric antigen receptor (UniCAR) T cells, and to better understand the impact of FAP on the immunotherapeutic treatment of solid tumors. First, we demonstrate the successful chemoattraction and infiltration of UniCAR T cells into the area of solid tumors, as well as the ability of UniCAR T cells to navigate through artificial extracellular matrix barriers. We further observe the synergistic efficacy of a dual-targeting UniCAR T cell approach against FAP and PSCA antigens, which represent the tumor microenvironment and the tumor, respectively. The results of our studies offer valuable methodologies and insights for engineering different 3D tumor models and studying immunotargeting of small-sized solid tumors (e.g., metastases and residual tumors). The developed microphysiological system has great potential to advance cancer research efforts aiming to elucidate the pivotal role of microenvironment in solid tumor development, enabling therapy trials and more precise prognosis for patients.

show abstract

3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy

Peng,

Janićijević,

Loureiro

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Investigating the complex interplay between fibroblast activation protein α-positive cancer associated fibroblasts and the tumor microenvironment in the context of cancer immunotherapy

Kraxner,

Braun,

Cheng

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionThis study investigates the role of Fibroblast Activation Protein (FAP)-positive cancer-associated fibroblasts (FAP+CAF) in shaping the tumor immune microenvironment, focusing on its association with immune cell functionality and cytokine expression patterns.MethodsUtilizing immunohistochemistry, we observed elevated FAP+CAF density in metastatic versus primary renal cell carcinoma (RCC) tumors, with higher FAP+CAF correlating with increased T cell infiltration in RCC, a unique phenomenon illustrating the complex interplay between tumor progression, FAP+CAF density, and immune response.ResultsAnalysis of immune cell subsets in FAP+CAF-rich stromal areas further revealed significant correlations between FAP+ stroma and various T cell types, particularly in RCC and non-small cell lung cancer (NSCLC). This was complemented by transcriptomic analyses, expanding the range of stromal and immune cell subsets interrogated, as well as to additional tumor types. This enabled evaluating the association of these subsets with tumor infiltration, tumor vascularization and other components of the tumor microenvironment. Our comprehensive study also encompassed cytokine, angiogenesis, and inflammation gene signatures across different cancer types, revealing heterogeneous cellular composition, cytokine expressions and angiogenic profiles. Through cytokine pathway profiling, we explored the relationship between FAP+CAF density and immune cell states, uncovering potential immunosuppressive circuits that limit anti-tumor activity in tumor-resident immune cells.ConclusionsThese findings underscore the complexity of tumor biology and the necessity for personalized therapeutic and patient enrichment approaches. The insights gathered from FAP+CAF prevalence, immune infiltration, and gene signatures provide valuable perspectives on tumor microenvironments, aiding in future research and clinical strategy development.

show abstract

Tumor Progression from a Fibroblast Activation Protein Perspective: Novel Diagnostic and Therapeutic Scenarios for Colorectal Cancer

Cited by 2 publications

References 52 publications

3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy

3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy

Investigating the complex interplay between fibroblast activation protein α-positive cancer associated fibroblasts and the tumor microenvironment in the context of cancer immunotherapy

Contact Info

Product

Resources

About