KEY TAKEAWAYS
- The study aimed to investigate the impact of PNI and nerve density within TME in HNSCC patients.
- Researchers noticed a pivotal role of sensory nerves in promoting HNSCC growth by suppressing Th1 CD4 T cells and activating CD8 T cells in the TME; further investigation is ongoing.
Perineural invasion (PNI) and heightened nerve density in the tumor microenvironment (TME) have consistently correlated with unfavorable outcomes in head and neck squamous cell carcinoma (HNSCC).
Laurel B. Darragh and the team aimed to delve into the intricate interplay between nerves within the TME, the adaptive immune system, and tumor growth progression.
Researchers performed an inclusive analysis utilizing RNA sequencing of human tumor tissue obtained from a recent HNSCC clinical trial and proteomic examination of human nerves derived from HNSCC patients. Additionally, syngeneic orthotopic murine models of HPV-unrelated HNSCC were employed to explore the intricate mechanisms through which sensory nerves influence the adaptive immune system.
Calcitonin gene-related peptide (CGRP) demonstrated a direct inhibitory effect on CD8 T cell activity in vitro. Notably, interventions that blocked sensory nerve function, including surgical, pharmacological, or genetic approaches, significantly increased CD8 and CD4 T cell activity in vivo.
The study concluded that sensory nerves actively contribute to accelerated tumor growth by directly impacting the adaptive immune system, resulting in decreased Th1 CD4 T cells and activated CD8 T cells in the TME.
These findings underscore the imperative for further investigation into the role of sensory nerves in HNSCC TME and suggest potential therapeutic benefits in blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to enhance treatment outcomes.
The study is sponsored by the NIH.
Source: https://pubmed.ncbi.nlm.nih.gov/38423011/
Darragh LB, Nguyen A, Pham TT, et al. (2024).’’ Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.’’ Med. 2024 Mar 8;5(3):254-270.e8. doi: 10.1016/j.medj.2024.02.002. Epub 2024 Feb 28. PMID: 38423011.
