Inhibitors of immune checkpoints—PD-1, PD-L1, CTLA-4—new opportunities for cancer patients and a new challenge for internists and general practitioners

Abstract

The treatment of cancer patients with immune checkpoint inhibitors (ICI) (anti-CTLA-4, anti-PD-1, anti-PD-L1, combined therapy anti-PD-1/PD-L1 with anti-CTLA-4) has without doubt been a significant breakthrough in the field of oncology in recent years and constitutes a major step forward as a novel type of immunotherapy in the treatment of cancer. ICIs have contributed to a significant improvement in the outcome of treatment and prognosis of patients with different types of malignancy. With the expansion of the use of ICIs, it is expected that caregivers will face new challenges, namely, they will have to manage the adverse side effects associated with the use of these drugs. New treatment options pose new challenges not only for oncologists but also for specialists in other clinical fields, including general practitioners (GPs). They also endorse the need for taking a holistic approach to the patient, which is a principle widely recognized in oncology and especially relevant in the case of the expanding use of ICIs, which may give rise to a wide variety of organ complications resulting from treatment. Knowledge and awareness of the spectrum of immune-related adverse events (irAEs) will allow doctors to qualify patients for treatment more appropriately, prevent complications, correctly recognize, and ultimately treat them. Additionally, patients with more non-specific symptoms would be expected, in the first instance, to consult their general practitioners, as complications may appear even after the termination of treatment and do not always proceed in line with disease progression. Dealing with any iatrogenic complications, will not only be the remit of oncologists but because of the likelihood that specific organs may be affected, is likely to extend also to specialists in various fields of internal medicine. These specialists, e.g., endocrinologists, dermatologists, pulmonologists, and gastroenterologists, are likely to receive referrals for patients suffering from specific types of adverse events or will be asked to provide care in cases requiring hospitalization of patients with complications in their field of expertise. In view of these considerations, we believe that there is an urgent need for multidisciplinary teamwork in the treatment of cancer patients undergoing immunotherapy and suffering the consequent adverse reactions to treatment.

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

“…Targeting and blocking PD-1 and its ligands, programmed cell death receptors ligand 1/2 (PD-L1/2), using monoclonal antibodies (mAb), is currently one of the most effective immunotherapy approaches for some cancers. Inhibition of the PD-1/PD-L1 system and, more generally, the immune checkpoint blockade has transformed and improved the management of neoplastic pathologies [1].…”

“…The inhibition of T cell-mediated immunity is also a strategy that cancer cells use to escape immune surveillance. Cancer cells have been found to upregulate inhibitory checkpoint molecules, resulting in suppression of cellular and humoral immunity [1,3]. Therefore, targeting and blocking PD-1/PD-L1, enhances T cell-mediated immunity against these cancer cells.…”

Tumor-Associated Macrophages: Key Players in Triple-Negative Breast Cancer

“…As a regulatory factor which limits killing effect of T cells, PD-1 is widely present in a variety of T cells (59)(60)(61)(62)(63). PD-L1 is the receptor of PD-1, which is mostly expressed on the surface of tumor cells and macrophages (61,(64)(65)(66). TNBC cells can highly express PD-L1 so that their T cell killing effect in the tumor environment is significantly inhibited (56,(67)(68)(69)(70).…”

The Current Application and Future Prospects of Astragalus Polysaccharide Combined With Cancer Immunotherapy: A Review

“…It is now well recognized that with the expansion of the use of ICIs, caregivers face new challenges in managing the adverse effects, such as diarrhea, fatigue, and itching, gastrointestinal complications, pancreatitis, hepatotoxicity, endocrinopathy, and so on (Wojtukiewicz et al, 2021).…”