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Therapeutic treatments targeting communication between angiogenic and immune microenvironments in thyroid cancers
Alessandro Prete1, Carmelo Nucera1,2
1Human thyroid cancers preclinical and translational research program, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Abstract:
Thyroid cancer treatment has recently been revolutionized by the introduction of specific targeted therapies (e.g. BRAFV600E or highly selective RET inhibitors), anti-angiogenic agents (e.g. tyrosine kinase inhibitors (TKIs)) and immune checkpoint inhibitors, which significantly ameliorate outcomes in selected groups of thyroid cancer patients. Targeted and anti-angiogenic treatments are characterized by transient and partial efficacy, due to primary or secondary tumor resistance mechanisms, and toxicity profile. Immune therapy-based approaches are producing preliminary results. Herein, we review and prospectively discuss immune microenvironment in non-medullary and medullary thyroid cancers and its interplays with angiogenic microenvironment (endothelial cells and pericytes). In addition, we discuss how these interactions might be targeted using combined therapies. Furthermore, we will review chimeric antigen receptor (CAR) T cells treatment that potentially may ensure a more durable and effective response in advanced thyroid cancers. In sum, angiogenic and immune microenvironments show functional connectivity in TCs. Therapies with anti-angiogenic and immune checkpoint inhibitors combined with specific targeted therapy inhibitors with a tolerable toxicity profile may overcome drug resistance and provide better clinical outcomes than single agents.
Insights
New thyroid cancer therapies, including targeted drugs and immune checkpoint inhibitors, show promise but face resistance. Combining these approaches may improve outcomes for thyroid cancer patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Thyroid cancer treatment has advanced with targeted therapies (e.g., BRAF, RET inhibitors), anti-angiogenic agents (tyrosine kinase inhibitors), and immune checkpoint inhibitors.
- Current targeted and anti-angiogenic treatments offer partial efficacy and face tumor resistance and toxicity challenges.
- Immune therapy shows preliminary but promising results in selected thyroid cancer patients.
Purpose of the Study:
- To review and prospectively discuss the immune microenvironment in non-medullary and medullary thyroid cancers.
- To explore the interplay between the immune and angiogenic microenvironments in thyroid cancers.
- To discuss novel combination therapies targeting these interactions and the potential of chimeric antigen receptor (CAR) T cells.
Main Methods:
- Literature review and prospective discussion of existing research on thyroid cancer microenvironments.
- Analysis of the functional connectivity between angiogenic and immune components within thyroid tumors.
- Exploration of therapeutic strategies, including combined therapies and CAR T cells.
Main Results:
- Thyroid cancers exhibit a functional connectivity between their angiogenic and immune microenvironments.
- Combined therapies involving anti-angiogenic, immune checkpoint, and targeted agents may overcome drug resistance.
- Chimeric antigen receptor (CAR) T cells present a potential avenue for durable and effective responses in advanced thyroid cancers.
Conclusions:
- The interplay between angiogenic and immune microenvironments is crucial in thyroid cancer progression and treatment response.
- Combination therapies targeting both angiogenic and immune pathways, alongside specific targeted therapies, offer a promising strategy to improve clinical outcomes.
- Targeted approaches like CAR T cells hold potential for more durable and effective treatment of advanced thyroid cancers.
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