Giuseppe Tarantino, PhD

I'm fundraising for IBD cures! I am participating in the 2025 Bank of America Chicago Marathon and raising funds for the Crohn’s & Colitis Foundation. With every mile, I hope to further their mission of finding cures for Crohn's di...

I'm running the Chicago Marathon with Crohn’s & Colitis Foundation Team Challenge to support those affected by Crohn's & Colitis. Join me in making a difference—every donation brings us closer to better treatments and a cure! 🏃‍♂️💙 Donate here:

teamchallenge.crohnscolitisfoundation.org/index.cfm?fu...

Overcoming Resistance Mechanisms to Melanoma Immunotherapy - American Journal of Clinical Dermatology The advent of immune checkpoint inhibition has revolutionized treatment of advanced melanoma. While most patients derive survival benefit from established immunotherapies, notably monoclonal antibodie...

In this review we summarizes recent advancements in melanoma immunotherapy with an emphasis on key tumor-intrinsic and -extrinsic mechanisms driving resistance.
#melanoma #immunotherapy #Resistance

link.springer.com/article/10.1...

Genomic heterogeneity and ploidy identify patients with intrinsic resistance to PD-1 blockade in metastatic melanoma Genomic features and models predict patients with aPD-1 intrinsic resistance who may benefit from combination ICB therapy.

10/10 What’s next?
- Applying these findings to liquid biopsy & target panel sequencing data.
- Testing in larger, independent cohorts.
Check out the full study here:
www.science.org/doi/10.1126/...

9/10 Clinical implications:
Our model provides additional predictive power beyond existing biomarkers like TMB and IFN-γ signatures.
It complements clinical features to better stratify patients for personalized immunotherapy

8/10 Independent validation:
Using paired targeted NGS panels (MSK-IMPACT):
- Ploidy estimates were consistent with WES.
- TNGS shows promise for broader clinical adoption.

7/10 Subtype insights:
Non-cutaneous melanoma subtypes (e.g., Acral, Mucosal) showed:
⬆️ Higher heterogeneity
⬆️ WGD incidence
Cutaneous melanomas exhibited heterogeneity driven by non-UV mutational processes.

6/10 Beyond response prediction:
- Timing of whole genome doubling (WGD) affects resistance: Tumors with recent WGD (high proportion of SNV with multiplicity of 2) showed high resistance despite low heterogeneity.

5/10 Model performance:
Our decision tree model using heterogeneity & ploidy achieved:
✅ High specificity (97%)
✅ Strong PPV (90%)
This helps identify patients unlikely to benefit from single-agent aPD-1 ICB, who might need combo therapies.

4/10 Why does this matter? integrating TCGA data we show that:
- Genomic heterogeneity predicts therapy resistance.
- Ploidy offers prognostic value.
Together, they provide a precise and independent biomarker system to improve clinical decision-making. 🔬

3/10 Main findings:
Across different cohorts, low ploidy 📉 and high heterogeneity 📈 robustly identify patients with intrinsic resistance to aPD-1 therapy

2/10 What we did:
- Harmonized data across independent metastatic melanoma cohorts.
- Focused on ICB-naïve patients treated with aPD-1 therapy.
- Used whole-exome sequencing (WES), bulkRNAseq and clinical annotations.

1/10🚨 New Findings Alert! 🚨
Discover how genomic heterogeneity and ploidy help predict intrinsic resistance to anti-PD-1 immune checkpoint blockade (ICB) in metastatic melanoma. 🧬https://www.science.org/doi/10.1126/sciadv.adp4670
📝 Key takeaways from our latest study: 🧵👇