Immunotherapy also called biologic therapy, is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function.
Cancer immunotherapy, due to its high anti-tumor efficacy, has attracted considerable attention globally from experts in various fields. However, immunotherapy could be severely toxic; not all patients may respond, thus requiring combination therapy. Therefore, a reasonable selection strategy for early treatment is urgently needed. It is vital to capture the dynamic, heterogeneous, and complex tumor behavior considering the absence of ideal companion biomarkers. Since tumor immune response involves tumor cells, several other cell types, and molecules in the tumor microenvironment, detection is very complex and variable. However, molecular imaging technology, namely the non-invasive whole-body molecular imaging by positron emission tomography and single-photon emission computed tomography, has shown considerable promise in tumor detection and cancer immunotherapy response. Identification of potential novel imaging biomarkers will allow a personalized treatment plan for every patient. Future imaging strategies for these molecules used alone or in combination or continuously, might help stratify patients before or during the early stages of immunotherapy, and might address the immunotherapy challenges encountered by the oncologists 1)
Immunotherapy may work by:
Stopping or slowing the growth of cancer cells
Stopping cancer from spreading to other parts of the body
Helping the immune system work better at destroying cancer cells
There are several types of immunotherapy, including:
Oncolytic virus therapy
The introduction of immunotherapy with immune checkpoint receptor blockade has changed the treatment of advanced cancers, at times inducing prolonged remission.
Emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiotherapy and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era.
Patients who receive immunotherapy (IT) alone may have an increased rate of Radiation induced necrosis RN/treatment-related imaging changes (TRIC) compared with those who receive chemotherapy (CT) or targeted therapy (TT) alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era 2).
Immunotherapy (i.e. immune checkpoints inhibitors) showed a significant impact on the prognosis of patients with metastatic melanoma, also in the setting of patients with brain metastases. Despite various possible treatments, survival of patients with melanoma brain metastases is still unsatisfactory; new treatment modalities or combination of therapies need to be explored. Being immunotherapy and radiotherapy alone both efficient in the treatment of melanoma brain metastases, the combination of these two therapies seems logical. Moreover radiotherapy can improve the efficacy of immunotherapy and the immune system plays a relevant role in the action of radiotherapy. Preclinical data support this combination. Clinical data are more contradictory 3).
Immune checkpoint inhibitors (anti-CLTA-4 antibodies and anti-PD-1/PD-L1 antibodies) potentiate the host's own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non-small cell lung cancer (NSCLC)-all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases 4).