Immuno-Oncology

When Immunity Meets Cancer

Cancer is a master of disguise, and the immune system is its vigilant yet sometimes confused sentinel. Early pioneers like James Allison demonstrated that releasing the brakes on T cells through CTLA-4 blockade could transform the immune system into a potent anti-cancer force. Tasuku Honjo revealed PD-1/PD-L1 as a critical checkpoint exploited by tumors to evade immunity. These discoveries painted a vivid picture: tumors are not passive targets—they actively manipulate immune surveillance, creating a high-stakes dialogue between biology and therapy.

Immune cells—dendritic cells (DCs), macrophages, and effector T cells—are the protagonists in this story. DCs present tumor antigens and instruct T cells, macrophages shape the tumor microenvironment, and T cells execute targeted killing. Understanding their choreography is essential for designing therapies that tip the scales toward tumor clearance while minimizing collateral damage.

Learning to Direct the Orchestra: My PhD Journey

During my PhD, I focused on harnessing immune instruction to combat tumors, particularly through DCs and tumor-associated macrophages (TAMs). Many tumors dysregulate the Wnt/β-catenin pathway, promoting stem-cell–like phenotypes, immune evasion, and resistance to immunotherapy.

In one study, we developed nanoparticle-based XAV939 (XAV-Np) to inhibit β-catenin in a mouse model of conjunctival melanoma. XAV-Np suppressed tumor cell viability, migration, and spheroid formation, while inducing immunogenic cell death (ICD) via HMGB1, calreticulin, and ATP release. Intra-tumoral delivery of XAV-Nps significantly reduced tumor progression, demonstrating that selective β-catenin inhibition can control growth and enhance tumor immunogenicity.

Extending these insights to the tumor microenvironment, XAV-Np treatment reprogrammed TAMs, enhancing CD80/CD86 expression, reducing PD-L1/CD206, and shifting cytokine production toward IL-6 and TNF-α. Co-culture with T cells increased CD8+ T cell proliferation, showing that targeting β-catenin in immune cells can amplify anti-tumor immunity.

Antony, F., Kang, X., ... & Suryawanshi, A. (2023). Targeting β-catenin using XAV939 nanoparticle promotes immunogenic cell death and suppresses conjunctival melanoma progression. International Journal of Pharmaceutics, 640, 123043.
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Pundkar, C., Antony, F., ... & Suryawanshi, A. (2023). Targeting Wnt/β-catenin signaling using XAV939 nanoparticles in tumor microenvironment-conditioned macrophages to promote immunogenicity. Heliyon.
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Looking Forward: These studies suggest that precise β-catenin inhibition in tumor cells and immune components could serve as a foundation for combination therapies, including checkpoint blockade and antigen-specific vaccines, to achieve durable, safe, and effective cancer control.

Industry Experience: Shaping the Future of Cancer Immunotherapy

The biotech industry is at an exciting inflection point. Clinical trials targeting neoantigens and personalized cancer vaccines are demonstrating that therapies can be tailored to a patient’s tumor landscape, moving beyond the one-size-fits-all approach of checkpoint inhibitors (e.g., NCT03815058, NCT03639714).

In my industry role, I worked on dendritic cell–based therapeutic vaccines, using model antigens to optimize T cell responses. While the focus was on translational development rather than discovery, this experience reinforced a key insight: the future of oncology lies in precision immune modulation, integrating tumor antigen specificity, immune cell orchestration, and high-throughput, scalable approaches.

The next generation of immuno-oncology strategies will combine:

• Tumor genomics and neoantigen identification

• Immune cell reprogramming (DCs, TAMs)

• Combination therapies with checkpoint inhibitors or cytokine modulation
  This integrated approach promises therapies that are not only effective but also precise, durable, and safe.

The Big Picture: Orchestrating Immunity

From mechanistic studies in the lab to translational industry work, a central principle has emerged: effective cancer immunotherapy is about orchestration, not brute force. By understanding DCs, macrophages, and T cells as a coordinated system, we can design interventions that amplify anti-tumor immunity while maintaining balance. Precision, timing, and context are key—whether in preclinical models or clinical translation.