As of 2018, pancreatic cancer has been the third leading cause of cancer deaths in the United States. With the recent trend of the utility of immunotherapy against cancer, pancreatic cancer should have been another candidate for such treatment. However, complications arise within the nature of the disease. In this article, we will try to shed light on these complications and look into the present situation of immunotherapy for pancreatic cancer. We will discuss future possibilities and setbacks for this therapy, along with why researchers are now focusing on this treatment as the next beacon of hope for our pancreatic cancer patients.
Pancreas and Cancer
As the pancreas has several functions for the body, the different parts and functions of the organ can exhibit various symptoms and severity. The pancreas mainly produces enzymes and hormones that process the food we eat. These enzymes and hormones change behavior when an abnormal formation of cells forms in the responsible area of the organ. For example, these are certain tumors that can affect the function of the pancreas:
- Gastrinoma: a tumor affecting the hormone that helps digest food called gastrin.
- Insulinoma: a tumor affecting the hormone that helps control sugar in the blood called insulin.
- Glucagonoma: a tumor affecting the hormone that increases sugar in the blood called glucagon.
Because of these effects on the function of the pancreas, the symptoms of these kinds of tumors are easily detectable. Unfortunately, these tumors are uncommon, and these only consist of 5% of pancreatic cancer cases. The more common types of pancreatic tumors are hard to screen and diagnose during its early stages. Diagnosis may only be conclusive when symptoms of the tumor growth have become apparent.
Current Treatments for Pancreatic Cancer
Due to this difficulty in the early diagnosis of pancreatic cancer cases, doctors are left to treat later stages of the disease. There are already several treatments for the disease, and the appropriate one depends on the cancer stage.
The effects of these treatments vary from pain relief to total cancer cure. For example, doctors may opt for radiation therapy and chemotherapy to inhibit the growth of cancer cells. A combination of the two, called chemoradiation therapy, can be more effective. Medical professionals may also opt for targeted therapy because these therapies can harm healthy cells around the tumor. Medicinal therapy, such as the use of specific drugs, can relieve the pain caused by other therapies.
The primary cure for pancreatic cancer is still surgical resection. Depending on the patient’s condition, the surgeon may only remove part of the affected parts of the organ or the whole of it. As cancer may have affected nearby organs, the procedure can also include removing parts of the stomach, small intestine, gallbladder, and spleen.
Why Immunotherapy for Pancreatic Cancer?
As described above, the pancreas still has a crucial function for the human body and those organs around it. Total removal of the affected organs may severely affect the patient’s quality of life after the surgery. Doctors do have some alternatives to this removal surgery through palliative surgery. However, this is only a treatment that alleviates the pain from the disease.
Because of these setbacks, researchers are currently looking into another alternative treatment. One that seems promising from recent studies is immunotherapy. This therapy involves using a patient’s immune system to fight off cancer cells.
Immunotherapy has had success in different malignancies. In 2012, a multicenter phase 1 trial for the anti-PD-L1 antibody, scientists administered the antibody to 207 patients with advanced cancer. They concluded that the mediation of the antibody resulted in durable tumor regression and prolonged stabilization of the disease. The cancers involved in the trial were melanoma, non-small lung, colorectal, renal-cell, ovarian, pancreatic, gastric, and breast cancer.
While this trial offered positive results in the field, recent studies on immunotherapy for pancreatic cancer say otherwise. Throughout the years, researchers have been starting to become aware of the hindrances between the two. This hindrance comes in the form of a complex microenvironment that pancreas cancer induces as the abnormal cells grow.
The Recent Findings In Immunotherapy For Pancreatic Cancer
Upon further research, the complications of immunotherapy for pancreatic cancer surface. In a 2018 review article, scientists quickly pointed out the effects of the immunosuppressive tumor microenvironment (TME) on the immunotherapy of pancreatic cancer. The TME consists of a cellular matrix of fibroblastic, vascular, and immune cells. This microenvironment causes poor infiltration of effector T cells and prominent myeloid inflammation. These heavily burden the process of immunotherapy for pancreatic cancer. At the same time, TME also disrupts drug delivery in certain treatments.
Despite this burden due to TME, researchers are still pushing for immunotherapy in pancreatic cancer. Some of these attempts include:
- Immune checkpoint blockade: inhibits specific T-cell regulatory molecules, promoting suppression of tumors through T-cells.
- Therapeutic vaccines: interacts with tumor cells, peptides, and proteins to drive tumor-specific T cells to eliminate tumors.
- Engineered T cells: modifies T cells using specific intermediaries, enhancing its capabilities to kill tumor cells.
- Agonistic immunotherapy: primes T cells through antigen-presenting cell agonists and T-cell agonists.
- Myeloid-based immunotherapy: specifically attacks the TME through specific white blood cells.
- Stroma-modulating immunotherapy: attacks the TME by targeting its stromal components.
Most of these therapies are still in the 2nd phase of their trials. One specific stroma-modulating immunotherapy has been finding success as of 2018. The use of hyaluronidase for stromal modulation is already in its third phase.
In a more recent study, scientists are now looking into the role of the microbiome in immunotherapy in pancreatic cancer. A 2019 review study showed that modulation of the microbiome could have an anti-cancer immune response against pancreatic cancer. Researchers have been thoroughly studying this since the early 20th century. They see that microbes have a role in immunity and cancer.
Because of all these studies, there is still hope for a better treatment alternative for pancreatic cancer. Although as of 2018, it still has an abysmal 5-year survival rate of 8%. Research will continue to push through whatever barriers a therapy may have.