The emergence of immunotherapy has shifted cancer treatment for patients with metastatic disease—cancer that has spread from its original location. Unlike therapies like chemotherapy that directly attack cancer cells, immunotherapy harnesses the body’s immune system to fight the disease. This approach has raised the possibility of a long-term solution for widespread cancer, though the answer remains multifaceted and is a subject of intense research.
The Mechanism of Immunotherapy Against Widespread Cancer
The immune system is a surveillance network with specialized cells that patrol the body to eliminate threats. This systemic reach makes it a promising weapon against metastatic cancer, a disease no longer confined to one location. Immunotherapy aims to direct this body-wide defense system to recognize and destroy cancer cells wherever they have traveled.
A primary strategy in immunotherapy involves drugs known as immune checkpoint inhibitors. Immune checkpoints are normal parts of the immune system, acting as brakes to prevent immune cells, particularly T-cells, from becoming overactive. Some cancer cells exploit this safety mechanism by producing high levels of proteins, such as PD-L1, that bind to proteins like PD-1 on T-cells. This effectively pushes a “stop” button, rendering the T-cells inactive against the cancer.
Checkpoint inhibitors work by physically blocking these connections. For instance, anti-PD-1 or anti-PD-L1 drugs prevent the tumor cell from deactivating the T-cell, thereby “releasing the brakes” on the immune response. This allows the T-cells to once again identify the cancer cells as a threat and mount an attack. Because T-cells circulate throughout the body, they can hunt down and eliminate tumor cells in distant organs.
Another approach is CAR T-cell therapy, where a patient’s own T-cells are extracted and genetically engineered to produce chimeric antigen receptors (CARs). These new receptors are designed to recognize a specific protein on the surface of cancer cells. The modified T-cells are then infused back into the patient, where they multiply and launch a targeted attack on the cancer. While currently used more for blood cancers, this method illustrates the principle of enhancing the immune system’s ability to destroy cancer throughout the body.
Defining a Cure in the Context of Metastatic Cancer
In oncology, the term “cure” is used with caution when discussing advanced cancers. The traditional definition implies the complete and permanent removal of every cancer cell from the body, ensuring it will never return. However, proving this with absolute certainty is nearly impossible, as a few undetectable cells could remain and cause a relapse years later.
Because of this uncertainty, clinicians use more precise terms to describe outcomes. A “complete response” or “complete remission” refers to the disappearance of all detectable tumors and cancer markers following treatment. While this is a major achievement, it does not guarantee the cancer is gone forever. The focus then shifts to the durability of this response.
A more practical goal is “durable long-term remission.” This describes a situation where a patient achieves a complete response that lasts for many years without needing further treatment. For individuals with what was once a terminal diagnosis, maintaining a cancer-free state for five or more years is a profound success. This state is often referred to as a “functional cure,” as the cancer is controlled so effectively that it no longer impacts the person’s lifespan or quality of life.
The conversation around immunotherapy has centered on achieving these durable remissions. The treatment’s ability to create a “memory” within the immune system means that after active treatment stops, the body may continue to police itself for new cancer cells. This potential for long-term control without continuous therapy is what distinguishes it from many conventional treatments.
Evidence of Long-Term Remission and Potential Cures
For a subset of patients, immunotherapy has produced results that challenge previous expectations for metastatic cancer. In certain cancer types, a minority of individuals have achieved remissions so durable they are increasingly considered cures. This has been most notable in cancers that were historically difficult to treat once they had spread.
Metastatic melanoma is a prominent success story for immunotherapy. Before checkpoint inhibitors, the prognosis for advanced melanoma was poor, with survival measured in months. With drugs like ipilimumab and pembrolizumab, a portion of patients now experience long-lasting responses. Clinical studies show that for patients with advanced melanoma, 5-year survival rates can be as high as 50%, with a subset remaining in remission at 10 years and beyond after stopping treatment.
Non-small cell lung cancer (NSCLC), the most common type of lung cancer, has also seen significant progress. For patients with metastatic NSCLC whose tumors express high levels of the PD-L1 protein, immunotherapy has become a frontline treatment. A percentage of these patients have achieved durable responses, with studies reporting 5-year survival rates approaching 20-30% in a population that previously had rates in the single digits.
Similar successes, though affecting a smaller percentage of patients, have been observed in other cancers. In advanced renal cell carcinoma (kidney cancer), combining different checkpoint inhibitors has led to high response rates and durable remissions. Likewise, in bladder cancer, a subset of patients who would have otherwise had a poor prognosis have achieved long-term survival. These examples provide evidence that for some, a functional cure for metastatic disease is a realistic possibility.
Factors Determining Treatment Success
The results of immunotherapy are not universal, and a focus of cancer research is understanding why some patients experience profound benefits while others do not. The success of the treatment depends on an interplay between the tumor, the patient’s immune system, and the therapy used. Scientists have identified several factors, called biomarkers, that can help predict the likelihood of a positive response.
One of the most established biomarkers is the expression of the PD-L1 protein on tumor cells. Since checkpoint inhibitors work by blocking the PD-1/PD-L1 interaction, a tumor with high levels of PD-L1 is often more susceptible to these drugs. The presence of PD-L1 suggests the cancer is already using this pathway to suppress the immune system, so blocking it can unleash a pre-existing but suppressed immune response.
Another factor is the Tumor Mutational Burden (TMB), a measure of the number of mutations within a tumor’s DNA. Cancers with a high TMB, such as melanoma and certain lung cancers, produce a greater number of abnormal proteins, or neoantigens. These neoantigens can make the cancer cells look more “foreign” to the immune system, increasing the chances that T-cells will recognize and attack them once immunotherapy drugs have released the brakes.
The overall health and composition of a patient’s immune system also play a part. The diversity of bacteria residing in the gut, known as the gut microbiome, has been shown to influence how well patients respond to immunotherapy. The specific type of cancer and its location in the body remain primary determinants, as some cancers are inherently more “immunogenic,” or capable of provoking an immune response.
Navigating Immunotherapy Treatment Challenges
While immunotherapy has created new possibilities, the treatment is not without challenges and potential complications. Unleashing the immune system to fight cancer can sometimes lead to unintended consequences when the newly activated immune cells begin to attack healthy tissues.
These side effects are known as immune-related adverse events (irAEs). Because the immune system can target any organ system, irAEs can manifest in many ways, often resembling autoimmune disorders. Common examples include:
- Colitis (inflammation of the colon)
- Pneumonitis (inflammation of the lungs)
- Hepatitis (inflammation of the liver)
- Thyroiditis (inflammation of the thyroid gland)
While many of these side effects are mild and can be managed with medications like steroids, some can be severe and, in rare cases, life-threatening.
Another challenge is treatment resistance. Resistance can be either primary, meaning the cancer never responds to immunotherapy, or acquired, where a tumor initially shrinks but later develops mechanisms to evade the immune system and begins to grow again. Cancer cells can evolve to stop expressing the biomarkers that the immune system targets, or they may activate alternative checkpoint pathways. Overcoming this resistance is a key area of ongoing research, exploring combination therapies and new drug targets.