Recently, a team of researchers from ISA Pharmaceuticals and the Leiden University Medical Center published an article in Nature Reviews Cancer that looked at findings from 250 peer-reviewed papers on immuno-oncology. The field has grown immensely in popularity over the past few years, with a large number of biotechnology firms and pharmaceutical companies undertaking research to develop the next step in cancer care.
What some people may not realize, however, is that the concepts behind immuno-oncology have been around for decades, and immunotherapy as a field has existed for centuries. As the researchers found, not all strategies have proven successful. Yet, at the same time, some avenues have shown potential for further research. This review of previous research helps scientists pinpoint what has been successful and what should guide their future projects.
One of the main, generalized strategies of immuno-oncology is to raise the number of tumor-specific T-cells capable of targeting, attacking, and destroying cancerous masses. In the majority of cases, this strategy has proven somewhat successful. The problem that researchers are now facing is the fact that increasing the availability of T-cells does not necessarily mean that these cells can perform their function within the microenvironment created by the tumor.
Cancer cells are extremely resilient and have developed means of suppressing the body’s immune response to keep themselves safe from attack. To that end, immuno-oncology approaches have proven most effective when this immunosuppression is not evident or when other treatments are used to counteract the immunosuppressive response.
The 3 Factors of Successful Cancer Immunotherapies
The researchers behind the study found three primary factors that almost all successful attempts at cancer immunotherapies had in common. The first of these factors is the use of tumor-associated antigens. These specific antigens are what allow the immune system to target the different tumors while leaving healthy cells unharmed. In general, cancers induced by viruses, like the human papillomavirus (HPV), can be targeted by antigens derived from that virus. Cancers of other origins require neoantigens, which are derived from mutations within the tumor cells. These antigens give the immune system directions about which specific cells to target.
The second factor vital to successful immunotherapy is the creation of a suitable environment for the attack. To produce the right immune cells, the body needs a balanced ratio of effector cells, including CD4 and CD8+ cells, and usually in large numbers. CD4 and CD8+ cells are both leukocytes: the former helps the immune system mount its attack against infections, while the latter actually carries out the attack and destroys cancer cells and other bodily invaders. In addition, the body requires a generation of memory T-cells. These are T-cells that have already encountered and responded to the cognate antigen, meaning that they are proven to target the cancer.
The third factor is the ability to address the immunosuppressive strategies of the specific tumor cells. Many cancer cells create a tumor microenvironment that stops regular immune responses through a range of different strategies. Two of the most common strategies for destroying this microenvironment and allowing for an immune response are chemotherapy and checkpoint blocking. Chemotherapy is used to irritate the immune system and throw it off balance so that it takes action—even in an immuno-suppressive microenvironment. This strategy is sort of like playing tug-of-war with the tumor and hoping to break down its defenses so that T-cells have the right conditions in which to act.
Checkpoint blocking has become a more common strategy in recent years. The body’s immune system has natural safety checks, which are useful when dealing with other types of disease because they prevent the immune system from damaging healthy tissue. However, these same blocks can prevent the immune system from attacking cancer cells because these cells can fool the system into thinking that they are healthy, normal cells. When the checkpoints are blocked, the body is able to once again attack and destroy tumor tissue.
When Is Cancer Immunotherapy Most Effective?
Immuno-oncology therapies have had varying degrees of success depending on the mode of implementation and the type of treatment used. As the review shows, immunotherapeutic vaccines alone have been proven useful against certain cancers, such as carcinoma in situ and residual disease, as well as premalignant disease. In progressive cancers, immunotherapies most commonly act to boost the effectiveness of more traditional treatments, such as chemotherapy.
However, recent advances have shown that immuno-oncology has the potential to redefine approaches to cancer treatment through personalized medicine. By focusing treatments according to the chemistry of each patient’s body and the biology of the cancer, immuno-oncology may become the primary form of treatment for certain cancers in the near future with traditional therapies serving as complementary treatments.
In short, more research needs to be done on how best to apply immunotherapy to fight cancer. The recently published study does a great job at pointing out where the field has been and sets a clear path for where researchers must go in the future. However, scientists need to look at more effective ways of integrating the three key factors of successful treatment. They can then evaluate which patients can benefit the most from this treatment and learn how to change the approach to benefit patients with other diagnoses.