The Synergy between Immuno-oncology and Traditional Cancer Treatments

Palucka Abbate^*
*Correspondence: Palucka Abbate, Department of Immunotherapy, Warsaw University of Life Sciences, 02-787 Warsaw, Poland, Email:

Introduction

Cancer remains one of the most complex and formidable challenges in modern medicine. Despite significant progress in early detection, diagnostics and treatment modalities, it continues to be a leading cause of mortality worldwide. For decades, traditional cancer treatments such as surgery, radiation therapy and chemotherapy have formed the foundation of oncologic care. These methods, while often effective, come with substantial limitations including toxicity, non-specific targeting and the development of resistance. The oldest and often most effective treatment for localized solid tumors. Allows complete removal of the tumor mass, providing immediate reduction in tumor burden. Not feasible for metastatic disease, risk of incomplete resection, post-surgical recurrence. Uses ionizing radiation to kill cancer cells by damaging their DNA. Highly effective for local control, often used as a curative or palliative modality. Can harm surrounding healthy tissues, provoke radiation resistance and lacks systemic [1].

The rise of immuno-oncology (IO) has revolutionized the cancer treatment landscape by harnessing the power of the immune system to detect and destroy cancer cells. Immune checkpoint inhibitors (ICIs), cancer vaccines and adoptive cell therapies like CAR-T cells have yielded unprecedented outcomes in certain malignancies. However, even these cutting-edge treatments are not universally effective and often benefit only a subset of patients [2].

Description

Immuno-oncology aims to unleash the bodyâ??s immune system to recognize and destroy tumor cells. Drugs like pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) remove inhibitory signals that dampen T cell responses. Includes CAR-T cells, TIL therapy and TCR-engineered T cells, which involve the ex vivo modification and reinfusion of immune cells. Stimulate the immune system to recognize tumor-associated antigens. Uses immune-activating molecules like IL-2 or IFN-alpha to boost immune responses. While transformative in some contexts, IO therapies face challenges such as tumor immune evasion, heterogeneity, limited response rates and immune-related adverse events (irAEs). Combining IO with traditional therapies is rooted in a deep understanding of tumor immunology and treatment biology. Chemotherapy and radiation can induce ICD, releasing tumor antigens and danger-associated molecular patterns (DAMPs) that prime immune responses. Radiation and some chemotherapies reduce immunosuppressive cells (e.g., Tregs, MDSCs), making the TME more conducive to immune activation. DNA damage increases neoantigen expression, enhancing tumor visibility to the immune system. Combining ICIs with cytotoxic agents can break through resistance mechanisms by disrupting tumor shielding. Anti-angiogenic therapy can normalize tumor vasculature, improving immune cell infiltration [3].

Numerous clinical trials have validated the efficacy of IO-traditional therapy combinations across different cancers. The KEYNOTE-189 trial demonstrated improved survival with pembrolizumab plus platinum-based chemotherapy vs. chemotherapy alone. Combined nivolumab and ipilimumab showed enhanced response rates but increased toxicity. Radiation has been used to augment IO responses in oligometastatic melanoma. Atezolizumab plus nab-paclitaxel improved progression-free survival in PD-L1+ TNBC. Nivolumab plus ipilimumab or axitinib has become standard for intermediate- and poor-risk RCC. Radiation combined with ICIs is under investigation to improve locoregional control and immune activation. Despite encouraging results, combination therapy is not without challenges: Additive or synergistic toxicity may lead to treatment discontinuation. Immune-related adverse events (irAEs) can complicate chemotherapy schedules. Identifying biomarkers (e.g., PD-L1 expression, TMB, MSI) to predict response is critical. Optimal scheduling (e.g., concurrent vs. sequential) remains an area of active research. Combination regimens are expensive, raising questions about cost-effectiveness and equitable access [4].

The field continues to evolve with novel combinations and technologies. EGFR or BRAF inhibitors combined with ICIs to exploit tumor vulnerabilities. Use of stereotactic body radiation therapy (SBRT) to prime immune responses. Engineered viruses that selectively kill tumor cells and stimulate immune responses. Targeted delivery of immunostimulatory agents or chemotherapy to reduce systemic toxicity. Gut microbiota influence IO efficacy; probiotics or fecal transplants may enhance responses. Predicting optimal combinations and personalizing therapy regimens. Integration of IO and traditional therapies is poised to become the new standard in oncology. Basket and umbrella trials to test combinations across molecular subtypes. Post-marketing studies to assess long-term outcomes and safety in diverse populations. Use of multi-omics, digital pathology and AI to guide tailored combination strategies. Exploring IO combinations before and after surgery to prevent recurrence. Multi-institutional efforts to harmonize treatment protocols and improve access [5].

Conclusion

The synergy between immuno-oncology and traditional cancer treatments represents a monumental shift in the way we approach cancer care. By leveraging the unique strengths of each modality, clinicians can design more effective, durable and patient-centric treatment regimens. While challenges remain-particularly in terms of toxicity, cost and complexity-the combined approach holds immense promise. Continued innovation, rigorous clinical research and integration of emerging technologies will be crucial in unlocking the full potential of this synergistic paradigm. As we enter a new era of combination oncology, the ultimate beneficiaries will be patients, who stand to gain longer, healthier lives through personalized and comprehensive cancer therapy.

Acknowledgement

None.

Conflict of Interest

None.

References

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