IMMUNO-ONCOLOGY: GENETICS OF TUMOR ESCAPE

“π•‹π•¦π•žπ• π•£π•€ 𝕖𝕧𝕠𝕝𝕧𝕖 𝕨𝕒π•ͺ𝕀 π•₯𝕠 π••π•šπ•€π•’π•“π•π•– π•šπ•žπ•žπ•¦π•Ÿπ•– π•£π•–π•€π•‘π• π•Ÿπ•€π•–π•€, 𝕠𝕗π•₯π•–π•Ÿ π•₯π•™π•£π• π•¦π•˜π•™ π•žπ•¦π•₯𝕒π•₯π•šπ• π•Ÿπ•€ π•₯𝕙𝕒π•₯ π••π• π•¨π•Ÿπ•£π•–π•˜π•¦π•π•’π•₯𝕖 π•’π•Ÿπ•₯π•šπ•˜π•–π•Ÿ π•‘π•£π•–π•€π•–π•Ÿπ•₯𝕒π•₯π•šπ• π•Ÿ 𝕠𝕣 π•¦π•‘π•£π•–π•˜π•¦π•π•’π•₯𝕖 π•šπ•Ÿπ•™π•šπ•“π•šπ•₯𝕠𝕣π•ͺ 𝕑𝕒π•₯𝕙𝕨𝕒π•ͺ𝕀.” - Prof. James P. Allison (Nobel Laureate)

🧬 Immuno-oncology leverages the immune system to fight cancer. Yet, tumors adapt through genetic mutations that disable immune recognition and foster escape. Understanding these mechanisms is essential for advancing precision therapies.

          πŸ”Ή Tumors mutate to downregulate antigens or MHC molecules, avoiding T cell detection. Intratumoral heterogeneity further ensures survival of immune-resistant clones.

          πŸ”Ή Overexpression of ligands like PD-L1 suppresses T cell activity via PD-1 engagement. Genetic alterations in these pathways underpin the rationale for checkpoint blockade therapies (e.g., anti-PD-1, anti-CTLA-4).

          πŸ”Ή Mutations driving secretion of IL-10, TGF-Ξ² and recruitment of Tregs/MDSCs remodel the microenvironment toward tolerance. This genetic reprogramming blunts anti-tumor immunity. Tumor microenvironment (TME)
Genetic alterations in pathways (e.g., Wnt/Ξ²-catenin, NF-ΞΊB) shift stromal-immune interactions, supporting escape and progression.

          ➡️ Genomic profiling now guides precised immunotherapy. High tumor mutational burden predicts better response to checkpoint blockade. Emerging strategies combine checkpoint inhibition with TME-modulating agents or CRISPR-based edits targeting escape pathways.

⚠️ In an Oystershell, tumor immune escape is a genetically driven, multi-layered process. By decoding these mechanisms, immuno-oncology is moving toward precision, combinatorial, and gene-targeted therapies, buffering the way for breakthroughs in cancer care.

Abubakar Abubakar ✍🏻

•  Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70.

•  Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707-723.

•  Binnewies M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24:541–550.

•  Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355.

•  Gettinger S, et al. Genetic determinants of response to PD-1 blockade. N Engl J Med. 2016;375:2109–2121.

#ImmunoOncology #CancerResearch #TumorEscape #PrecisionMedicine #Genomics #CancerGenetics #CancerTherapy #OncologyInnovation #ImmuneCheckpoint #CancerImmunology #CRISPR #TranslationalMedicine #IVF #ART #NGS #PersonalizedMedicine #Biotech #FutureOfCancerCare πŸ”¬πŸ’‰⚕️

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