Immunotherapy for cancer treatment has recently become an alternative approach to cancer treatment using the patients’ immune system to fight cancer cells. Most of the current immunotherapies for cancer are focused on targeting the PD-1 pathway. PD-1 inhibitors have been evaluated in multiple cancer types and may be considered among available treatment options depending on the clinical setting, significant variability exists among cancer types and patients, thereby limiting their clinical efficacy.
Understanding the PD-1 Pathway
These tissues are protected by several different immune suppression pathways. PD-1 is a cell surface protein which is expressed by T cells under certain conditions. Its interaction with specific ligands such as PD-L1 can inhibit T cell immunity. Some cancer cells express PD-L1 and use this pathway to avoid destruction by the immune system.Tislelizumab as a PD-1 monoclonal antibody that blocks the PD-1 receptor on T cells, helping restore antitumor immune responses.
By interfering with the communication between cancer cells and cells of the immune system that use the PD-1 pathway to avoid an immune response, cancer immunotherapies can allow T-cells to recognize and kill cancer cells.
These medicines are called PD-1 inhibitor, and they work by blocking the interaction of PD-1 and its ligands. Although these medicines can be very effective in treating cancer, each patient is different and as a result, it is very important to choose the right treatment for the individual and to monitor them for adverse effects.
Why Patient Selection Matters
Immunotherapy has many different applications in treating cancer. Different patients can benefit from different types of treatment, and even in cases where there are promising results, cancer can recur. Even within the same cancer type, tumors can have vastly different characteristics that affect their response to treatment.
When it comes to treating cancer with immunotherapy, a number of factors can determine the appropriateness of cancer treatment using immunotherapy. An important factor is the type of cancer and the stage at which it has been detected. Other factors include prior cancer therapy, the patient’s general state of health, and characteristics of the tumor itself. There are also specific biomarkers that can be useful for determining the suitability of cancer patients for treatment with immunotherapy.
Other cancer types are tested for the cancer patient for other biomarkers like the microsatellite instability (MSI) and/or the mismatch repair (MMR) protein deficiency. As with the PD-1 pathway biomarkers, the tests for these biomarkers can give the cancer doctor more information on how the cancer patient is going to react to a PD-1 inhibitor-based cancer treatment.
Combining Immunotherapy with Other Treatments
Growing interest in PD-1-based approaches has led to their combination with other cancer treatments including chemotherapy, radiation therapy, and targeted agents, as well as with other immunotherapies.
Different cancer treatments can work to kill cancer cells by entirely different mechanisms. So for example, a treatment that kills tumor cells and another that enables the immune system to recognize and kill tumor cells could be used in combination.
Combination treatment strategies are being studied in various cancers and require assessment of both potential benefits and risks. Thus, assessing potential benefits and potential harm of a treatment combination is very important and is not necessarily better than a single agent.
Monitoring Treatment Response
Monitoring of the effect of immunotherapy in cancer treatment can sometimes be difficult to assess in comparison to other treatments of cancer. To assess the success of the treatment, for example, an imaging study, analysis of samples from the affected tissue, the physical examination of the patient as well as an assessment of the symptoms that affect the patient are necessary.
Radiological changes, not immediately indicative of failure to control disease can occur as a result of treatment-induced immune activity that requires a period to clarify. Conversely, true progression of disease can occur. Keeping a record of your symptoms, either on your own or with your doctor, is very important. Not only will this help monitor whether your cancer is getting better or worse, but also any changes in your symptoms or the development of new ones should be reported to your doctor immediately.
Managing Immune-Related Side Effects
These events occur when the enhanced immune system is mistakenly directed to attack healthy parts of the body. As with any serious medication, there are potential side effects associated with the use of immunotherapy to treat cancer.
Sometimes it can cause problems with other organs including the skin, GI tract, liver, lungs and endocrine organs. Symptoms can range from mild to severe and even potentially life-threatening.
Identifying an immune-related adverse event very early on is crucial. Even though it may not be serious at first, it could become more serious if left untreated. Patients must be aware of their symptoms and inform their physician or the study team immediately if they get worse. Treatment of immune-related side effects is related to the severity of the complications and the organs involved. In case of minor side effects, treatment with medication may be sufficient. In more severe cases, however, it may be necessary to withdraw immunotherapy for a while.
Emerging Evidence and Ongoing Research
Ongoing research has shown that combinations of PD-1-based treatments as well as different treatment sequences, new biomarkers and approaches to overcome resistance of tumors to cancer therapy are potential strategies to improve current cancer therapies.
It is also critical to understand why tumors initially responsive to treatment become resistant to PD-1 pathway inhibition. Tumor evolution and changes in the immune environment are just a few of the possible reasons for resistance to these therapies.
Several clinical trials are exploring strategies to enable ongoing tumor control such as combining PD-1/PD-L1 pathway inhibitors with other immune-checkpoint inhibitors, with targeted therapies, with cancer vaccines, and/or with other classes of drugs to modify the tumor environment.
The Role of Individualized Treatment
Personalized treatment approaches are an active area of oncology research and the emerging variety of cancer immunotherapies are designed to be individualized and tailored for the individual patient with cancer, in order to derive maximum clinical benefit from available and emerging treatments for cancer.
By tailoring cancer treatment to the individual, there is hope that more patients can benefit from treatment while minimizing exposure to treatments that will have little benefit to the individual.
Oncologists should be consulted about the use of PD-1-based therapies. Important background information can be derived from clinical studies, but the results of these must not be applied “blindly” to all patients suffering from a given type of cancer.
Looking Ahead
Current research into the use of PD-1-based therapies is directed at establishing which patients are most likely to benefit from treatments and at managing resistance to, and side effects of, immunotherapy.
The ultimate objective of ongoing research is to develop the cancer immunotherapy to become more precise, more effective and more appropriate to use on individual patients. In order to achieve this, appropriate use of the treatment must be made for individual patients, and monitoring of the treatment must be carried out under close communication with patients.
