Home » Emerging Immunotherapies for NETs
Neuroendocrine tumours (NETs) present unique challenges in cancer treatment due to their diverse biology and often slow-growing nature.
While traditional therapies like surgery, chemotherapy, and targeted treatments have shown effectiveness in managing NETs, immunotherapy—a rapidly evolving field in oncology—offers new hope.
This article explores emerging immunotherapies for NETs, their mechanisms, current research, and future potential.
Neuroendocrine Cancer Australia (NECA), is dedicated to supporting individuals diagnosed with NETs, and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.
Immunotherapy harnesses the body’s immune system to recognise and destroy cancer cells. Unlike traditional treatments that directly target tumours, immunotherapy boosts the immune system’s natural defences, enabling it to identify cancer cells as threats and attack them more effectively.
Key mechanisms of immunotherapy include:
Traditional cancer treatments, such as chemotherapy and radiation, target rapidly dividing cells but can affect healthy tissues, leading to significant side effects. Immunotherapy, in contrast, focuses on modulating the immune system, offering the potential for longer-lasting responses with fewer systemic side effects.
However, its effectiveness varies across tumour types, including NETs, where the unique biology poses additional challenges.
Understanding the body’s reaction to immunotherapy is constantly evolving. However, there still exist some challenges when undertaking this kind of treatment, especially with regards to NETs.
NETs are a heterogeneous group of cancers that arise from hormone-producing neuroendocrine cells. Their slow-growing nature and low tumour mutational burden (TMB) can make them less likely to trigger an immune response, reducing the effectiveness of many immunotherapies.
NETs have evolved mechanisms to evade the immune system, such as low expression of tumour-specific antigens and reduced presentation of these antigens on their surface. This immune evasion makes it difficult for immunotherapies to recognise and target NET cells effectively.
The tumour microenvironment (TME) in NETs is characterised by immunosuppressive cells and cytokines that inhibit immune responses. Components like regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) dampen the effectiveness of immunotherapies, creating a hostile environment for immune activation.
Checkpoint inhibitors are a leading form of immunotherapy in cancer treatment. They block immune checkpoint proteins like PD-1, PD-L1, and CTLA-4, which normally act as brakes on T-cell activity.
While checkpoint inhibitors have shown success in other cancers, their effectiveness in NETs has been limited. Early clinical trials suggest modest responses, particularly in high-grade, poorly differentiated NETs. Combination strategies with other therapies are being explored to enhance efficacy.
Cancer vaccines aim to stimulate the immune system to target specific tumour-associated antigens. These vaccines introduce antigens to the immune system, prompting it to recognise and attack tumour cells expressing these proteins.
Research is underway to identify tumour-specific antigens in NETs which could serve as vaccine targets. The challenge lies in selecting antigens that are highly expressed in NETs but absent in normal tissues to minimise side effects.
Though still experimental, cancer vaccines hold promise in NETs by activating immune responses that are typically weak in these tumours. Early trials have shown potential in enhancing immune recognition, but more research is needed to optimise their design and delivery.
Adoptive cell therapy involves collecting, modifying, and reintroducing a patient’s immune cells to enhance their tumour-fighting capabilities.
Research on T-cell-based therapies for NETs focuses on expanding T-cells that naturally recognise NET-specific antigens or engineering T-cells to target these antigens more effectively.
Chimeric antigen receptor (CAR) T-cell therapy, which has revolutionised treatment for some blood cancers, is being explored for NETs. By engineering T-cells to express receptors specific to NET antigens, CAR-T therapy offers a promising avenue for targeting resistant tumours.
As with many cancer treatments, the best results from immunotherapy often come with a combination of therapies. Your primary care team will advise on the best combination of therapies for your circumstances.
Combining immunotherapy with targeted treatments, such as peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSA), is a growing area of research. These combinations aim to enhance immune activation while simultaneously targeting tumour cells with precision therapies.
Chemotherapy and radiation can alter the tumour microenvironment, making it more susceptible to immunotherapy. By releasing tumour antigens during cell death, these treatments may enhance the immune response when paired with checkpoint inhibitors or vaccines.
Not all patients respond to immunotherapy. Biomarkers are crucial for identifying those most likely to benefit. Biomarkers such as PD-L1 expression and tumour mutational burden (TMB) can predict response rates and guide treatment selection.weeq
Case studies have highlighted instances where NET patients have achieved durable responses to immunotherapy, particularly in high-grade NETs. These successes underscore the potential of immunotherapy in specific subsets of NETs.
Despite these advances, achieving consistent and durable responses in NETs remains a challenge. Factors like tumour heterogeneity, immune evasion, and the immunosuppressive tumour microenvironment hinder the long-term success of immunotherapy.
Ongoing research aims to develop new immunotherapies tailored to the unique biology of NETs. Innovations include bispecific antibodies that simultaneously target tumour cells and activate immune cells, as well as next-generation checkpoint inhibitors with enhanced specificity.
Personalisation is the future of cancer treatment. For NET patients, combining genomic profiling with immunotherapy could allow for treatments that are customised to the tumour’s molecular and immunological characteristics.
Clinical trials are essential for advancing immunotherapy in NETs. Efforts to expand trial availability and ensure global access to emerging treatments will be critical in bringing these innovations to patients worldwide.
Immunotherapy represents an exciting frontier in the treatment of neuroendocrine tumours. While challenges remain, ongoing research and innovations hold promise for improving outcomes and expanding options for NET patients. For more information on immunotherapy and its role in NET care, patients are encouraged to consult with their healthcare team or connect with Neuroendocrine Cancer Australia for support and resources.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.