Understanding complex interactions between cancer and the nervous system may offer new insights into the mechanisms that drive tumour progression
Growing evidence that the nervous system can influence tumour behaviour highlights the need to better understand the biological basis and consequences of interactions between cancer cells and the host, both to elucidate mechanisms of disease progression and to identify new therapeutic opportunities (Nature 2023;618:467–479). However, the neuroscience of cancer remains comparatively underexplored today. A key challenge for this emerging field is to identify unifying principles that control tumour–nervous system communication and determine whether these interactions follow a predictable biological logic.
Recent studies illustrate the diverse mechanisms through which neural signalling can influence tumour biology. In small cell lung cancer (SCLC), intrinsic electrical activity within the classic neuroendocrine-high subtype of the tumour cells was shown to directly promote tumour progression (Nature 2025;639:765–775). Neuroendocrine cancer cells were metabolically supported by non-neuroendocrine cancer cells, revealing functional cooperation between distinct cancer cell subtypes. As SCLC progresses, cancer cells develop elevated neuronal features, suggesting that a tumour-autonomous positive feedback loop is established. Complementing these findings, a study of lung adenocarcinoma identified a neuroimmune mechanism through which sensory neurons regulate tumour progression (Cell 2026;189:4276–4294). In this research, tumour-associated nociceptive neurons released neuropeptide calcitonin gene-related peptide (CGRP), which acted on tumour-associated macrophages to suppress tertiary lymphoid structure (TLS) formation. Disrupting this sensory neuron–CGRP axis restored TLS formation, enhanced immune responses and suppressed tumour growth. Pharmacological inhibition of CGRP also improved responses to immune checkpoint blockade, highlighting a potential therapeutic opportunity for targeting neural regulation of the tumour microenvironment.
However, it remains unclear whether these mechanisms are conserved across cancer types, and the situation is further complicated by reports of opposing pro- and antitumour effects of neural signalling within the same cancer (Cell Oncol (Dordr). 2026;49:35). One approach to resolving this complexity is to examine pairs of adenocarcinoma and neuroendocrine tumours across lung and pancreatic cancers to distinguish effects associated with tissue-specific innervation from those determined by tumour lineage and genetics.
Looking ahead, a key focus of the field will be understanding how neural and immune pathways interact to shape tumour progression and therapeutic response. Evidence suggests that neuroimmune interactions may be an important component of the tumour microenvironment, raising the possibility of targeting neural signalling alongside immunotherapies. This may be particularly beneficial for immunologically ‘cold’ tumours that respond poorly to immune checkpoint blockade. If neural signalling can be manipulated to promote the recruitment and activation of immune cells, this could provide a mechanism for converting ‘cold’ tumours into immune-responsive ‘hot’ tumours. Whereas tumour-intrinsic characteristics, such as driver mutations or tumour mutational burden (TMB), may be difficult to modify therapeutically, neural signalling and its effects on the tumour microenvironment may represent a more tractable opportunity for intervention.
Beyond biology, establishing effective interdisciplinary collaborations will be essential in advancing the field of cancer neuroscience. Currently, there is a need for greater integration between cancer biologists, immunologists and neuroscientists through the adoption of common experimental approaches, terminology and frameworks for interpreting data that overcome historical disparities between the disciplines. Turning individual observations into a more systematic approach will help us to understand how neural, immune and tumour signalling pathways interact to determine disease progression and treatment response.
Programme details
Li L. Cancer and the peripheral nervous system. MAP Congress 2026 - Keynote lecture
