Discover how groundbreaking advances in cancer immunotherapy are training our body's natural defenses to combat malignant cells.
Imagine that our own body possesses a powerful internal weapon against cancer — a sophisticated system capable of recognizing and destroying malignant cells. Until recently, this seemed like science fiction, but today, oncoimmunology is turning this dream into reality 1 .
After a period of stagnation, oncology has found "new breath" and in the last 20-25 years has been enriched with knowledge that can truly be called revolutionary 1 . At the intersection of oncology and immunology, innovative treatment methods are emerging that are radically changing approaches to the therapy of malignant diseases.
Harnessing the body's natural defense mechanisms to fight cancer cells.
Precisely targeting cancer cells while sparing healthy tissues.
At the core of immunotherapy lies the concept of the "anti-tumor immune cycle" — a cascade of processes responsible for the immune system's response to tumor cells 2 . This cycle includes several key stages:
Detection of tumor antigens by immune cells
Triggering of specific immune response
Direction of immune cells to the tumor site
Penetration into the tumor microenvironment
Elimination of cancer cells
Cancer cells are masters of disguise. They can "hide" from the immune system using various strategies:
Modern oncoimmunology focuses on two well-studied types of immunotherapy 2 :
| Type of Therapy | Mechanism of Action | Examples | Advantages | Limitations |
|---|---|---|---|---|
| Checkpoint Inhibitors | Blocking inhibitory signals in immune synapses | Nivolumab, Ipilimumab | Broad spectrum of action across various tumors | Risk of autoimmune complications |
| Adaptive Cell Therapy | Administration of artificially activated immune cells | CAR-T therapy | High specificity | Complex manufacturing, high cost |
| Cytokine Therapies | Systemic activation of immune response | Interleukin-2 (Roncoleukin®) | Approved for use since 1995 | Toxicity with systemic administration |
One of the turning points in oncoimmunology was the study of combination therapy for metastatic melanoma — an aggressive form of skin cancer with an extremely poor prognosis. Researchers hypothesized that a combination of two checkpoint inhibitors — nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) — would be more effective than monotherapy, as these drugs act on different stages of T-lymphocyte activation 2 .
The study was conducted as a randomized controlled trial with participants having untreated melanoma without BRAF mutation. The experimental protocol included:
| Efficacy Parameter | Nivolumab + Ipilimumab | Nivolumab | Ipilimumab |
|---|---|---|---|
| Overall Survival (12 months) | 73% | 65% | 53% |
| Objective Response Rate | 58% | 44% | 19% |
| Complete Response | 19% | 12% | 5% |
| Median PFS (months) | 11.7 | 6.9 | 2.9 |
| Adverse Event | Nivolumab + Ipilimumab | Nivolumab | Ipilimumab |
|---|---|---|---|
| Any Grade 3-4 Side Effects | 59% | 21% | 28% |
| Colitis | 13% | 2% | 9% |
| Increased ALT/AST | 13% | 4% | 2% |
| Diarrhea | 12% | 3% | 8% |
This study became an important milestone in oncoimmunology for several reasons:
Confirmed hypothesis about synergism of different immunotherapeutic approaches
Demonstrated possibility of achieving long-term remissions in metastatic melanoma
Highlighted importance of balance between efficacy and toxicity
Stimulated development of biomarkers for predicting response and toxicity
The results of this research led to regulatory approval of the nivolumab and ipilimumab combination for melanoma treatment and changed the standards of therapy for this disease.
Modern oncoimmunology relies on a sophisticated arsenal of research tools. Here are the main categories of reagents and materials used in this field:
Used both for therapy (checkpoint inhibitors) and for research on immune response mechanisms. Therapeutic antibodies block inhibitory signals (PD-1, CTLA-4) or activate stimulating receptors on immune cells.
Proteins that regulate the growth and activity of immune cells. Interleukin-2 (IL-2) is one of the first cytokines used in cancer immunotherapy. The drug Roncoleukin® (recombinant human interleukin-2) has been approved for use since 1995 and demonstrates effectiveness in various diseases 3 .
T-lymphocytes, NK cells, and dendritic cells are used to study immune response mechanisms and develop adaptive cell therapies. Improving methods for expanding and activating these cells ex vivo is a key research direction.
Include transgenic mice with human immune systems, organoids, and 3D cultures that reproduce complex interactions in the tumor microenvironment. Modern models increasingly adequately mimic human immune responses, improving the predictive value of preclinical studies.
Flow cytometry and immunohistochemistry allow assessment of tumor immune cell infiltration, checkpoint molecule expression, and lymphocyte activation status. The developing "Immunoscore" — a system for quantitative assessment of immune response in tumors — has the potential to become an important prognostic tool .
Quantitative analysis of cell populations
Spatial analysis of immune cell distribution
Quantitative assessment of immune response
Oncoimmunology is experiencing a golden era of discoveries, but it faces serious challenges. Resistance to therapy remains a significant problem — even with the most modern approaches, some patients do not respond to treatment . Resolving this issue requires a deeper understanding of resistance mechanisms and the development of strategies to overcome them.
Various immunotherapeutic combinations to enhance anti-tumor response
Using genomic profiling and biomarkers for treatment selection
Investigating the influence of microbiome on immunotherapy efficacy
Using not only T-cells but also NK cells and macrophages
"A cure for cancer may be an unrealistic goal, but achieving long-term disease control is becoming an increasingly achievable task" .
Oncoimmunology offers a fundamentally new approach to cancer treatment based on mobilizing the body's internal resources. With continued research and method refinement, immunotherapy promises to become even more effective and accessible for patients with various types of malignant diseases.
Became an important milestone in the exchange of knowledge and ideas in this rapidly developing field, contributing to further progress in the fight against oncological diseases.