Immunotherapy is a treatment method that strengthens or directs the body’s own immune system to fight cancer cells. It has been one of the greatest revolutions in cancer treatment over the last decade and has radically changed treatment outcomes in many cancer types.
Immune Checkpoint Inhibitors
Cancer cells hide themselves by using the immune system’s “brake” mechanisms. Immune checkpoint inhibitors — such as pembrolizumab, nivolumab, and atezolizumab — release these brakes, allowing immune cells to recognize and destroy cancer cells. They have become part of standard treatment in lung cancer, melanoma, bladder cancer, head and neck cancers, and many other cancer types.
How does the brake mechanism work?
T cells, the main warriors of our immune system, are responsible for recognizing and destroying abnormal cells in the body. However, natural brake points exist so that this system does not go too far — just like a car has both an accelerator and a brake. PD-1/PD-L1 and CTLA-4 are the most important of these brakes. Over time, cancer cells learn to press these brakes, numb T cells, and present themselves to the immune system as “harmless.” These inhibitors come into play exactly at this point, releasing the brake and allowing T cells to wake up again.
How is it different from chemotherapy?
While chemotherapy tries to directly target and kill the cancer cell, immune checkpoint inhibitors target the immune system rather than the tumor. This fundamental difference makes the two treatment classes complementary. When used together with chemotherapy, chemotherapy breaks tumor cells apart and releases antigens; this further strengthens the immune response. It has also been proven that they can have synergistic effects with targeted therapies, anti-VEGF agents, and radiotherapy.
Treatment response and curative potential
Perhaps the most striking difference is the course of the treatment response. When chemotherapy is stopped, the tumor often starts to grow again, whereas immune checkpoint inhibitors can provide lasting protection in some patients even after treatment has ended. Once the immune system has been “trained,” it can continue to recognize and destroy the tumor. Long-term data in melanoma and lung cancer show that in some patients, complete responses lasting for years — a picture effectively overlapping with cure — can be achieved.
Limitations: It does not work in every patient. PD-L1 expression, tumor mutational burden, and MSI status are the main biomarkers used to predict who will benefit from this treatment. On the other hand, because they activate the immune system, they have a distinct side-effect profile: immune-mediated side effects such as pneumonitis, colitis, and thyroiditis require careful clinical monitoring.
Adoptive Immunotherapy
This involves multiplying or strengthening the patient’s own immune cells in the laboratory and giving them back to the patient. TIL — tumor-infiltrating lymphocyte — therapy is the best-known example of this approach. Promising results are being achieved especially in advanced melanoma and some solid tumors.
Basic logic
Our immune system can actually recognize cancer cells — the problem is that this recognition is often insufficient. The tumor microenvironment suppresses, exhausts, and disables immune cells. Adoptive immunotherapy solves this problem from a different angle: it takes cells capable of fighting the patient’s own tumor, multiplies them into billions of copies in the laboratory, genetically strengthens them if necessary, and then gives them back to the patient.
Difference from checkpoint inhibitors
While checkpoint inhibitors remove the obstacle in front of existing immune cells, adoptive immunotherapy produces completely new and strengthened cells. Therefore, it may be effective even in patients who do not respond to checkpoint inhibitors or who have insufficient numbers of immune cells. The two approaches are not competitors but complements.
Its applicability to solid tumors is still more limited compared with hematologic cancers; however, clinical trials are accelerating in many solid tumors, especially ovarian cancer, lung cancer, and colorectal cancer.
CAR-T Cell Therapy
The patient’s T cells are collected, genetically reprogrammed, and designed to recognize and destroy cancer cells. These “super soldiers” are given back to the patient to fight cancer. Groundbreaking results have been achieved especially in blood cancers and lymphomas, and research on solid tumors continues rapidly.
How does it work?
Normal T cells cannot recognize every cancer cell. In CAR-T therapy, an artificial “radar” is added to these cells to recognize a specific protein on the tumor surface — for example, CD19 in B-cell cancers. These cells then directly attack when they see their target and also multiply to amplify the attack.
Where is it used?
FDA-approved products are available in diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma; durable complete responses can be achieved even in patients who have relapsed many times. In solid tumors, effectiveness is still more limited due to the suppression caused by the tumor microenvironment, but clinical trials are accelerating.
Limitations: The treatment process requires intensive resources, and serious side effects — especially cytokine release syndrome and neurotoxicity — make close monitoring mandatory. Nevertheless, the durable responses achieved in patients who have exhausted standard treatments make this field one of the most promising fronts in oncology.
Cancer Vaccines
Cancer vaccines train the immune system to recognize and attack specific cancer cells. Personalized cancer vaccines developed with mRNA technology are produced specifically for each patient’s tumor.
Difference from classic vaccines
Influenza or COVID vaccines are given to prevent disease. The vast majority of cancer vaccines, however, are therapeutic — that is, they are used to activate the immune system against the tumor when cancer has already developed. Each tumor has proteins on its surface that differ from healthy cells — neoantigens. The vaccine teaches the immune system this fingerprint and activates T cells.
Why has mRNA technology revolutionized this field?
The genetic profile of the tumor is analyzed through sequencing, patient-specific mutations are identified, and mRNA sequences designed to generate an immune response against these mutations are created. These personalized vaccines, which can be produced within a few weeks, are truly “custom-made” treatments produced separately for each patient. In phase 2 studies conducted by BioNTech and Moderna in melanoma, a significant reduction in recurrence risk was achieved in combination with pembrolizumab.
Oncolytic Virus Therapy
Genetically modified viruses selectively infect and destroy cancer cells. These viruses both directly kill cancer cells and stimulate the immune system against the tumor. It has received FDA approval in melanoma treatment, and clinical trials continue in other cancer types.
Clinical use
Talimogene laherparepvec — T-VEC — is the first oncolytic virus derived from herpes simplex virus and approved by the FDA in advanced melanoma. Injected into the tumor, T-VEC both destroys the local tumor and may create responses even in distant metastases that are not injected — this “abscopal effect” is one of the most striking features of the treatment.
Combination potential
Oncolytic viruses show particularly strong synergy in combination with checkpoint inhibitors. The virus “heating up” the tumor microenvironment — that is, drawing immune cells into the tumor — may increase the effectiveness of immune checkpoint inhibitors.
Cytokine Therapies
Cytokines are protein molecules that enable immune cells to communicate with one another. Cytokines such as interleukin-2 — IL-2 — and interferon are used in treatment to strengthen the immune response. New-generation cytokine therapies aim to achieve a stronger immune response with fewer side effects.