Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy.
Overview
and 12 other authors
Saroj Rajput8, Asish Pal6, Arindam Maitra3, Santiswarup Singha2, Rajesh Panwar7, Satish Khurana4, Ujjaini Dasgupta9, Sandeep K. Bhoriwal7, Jyothi S. Prabhu10, Prasenjit Das7, Veena S. Patil2, Avinash Bajaj1- Laboratory of Tumour Immune Microenvironment (TIME), Regional Centre for Biotechnology, 3rd Milestone Faridabad Gurgaon Expressway, Faridabad 121001, India
- National Institute of Immunology, Aruna Asif Ali Marg, New Delhi 110067, India
- National Institute of Biomedical Genomics, Kalyani 741251, India
- School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram 695551, India
- Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurgaon 122413, India
- Institute of Nanoscience and Technology, Sector 81, Sahibzada Ajit Singh Nagar, Mohali 140306, India
- All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
- ESIC Medical College and Hospital, New Industrial Town, Faridabad 121012, India
- Koita Centre for Digital Health, Trivedi School of Biosciences, Ashoka University, Sonipat 131029, India
- St. John’s Research Institute, 100 Feet Rd, John Nagar, Koramangala, Bengaluru 560034, India
Abstract
We report presence of cholinergic nerve fibers in the periphery and stroma of colon cancer tissues and their correlation with poor T cell and increased macrophage infiltration. We employed hydrogel-mediated localized delivery of an FDA-approved local anesthetic, bupivacaine (BUP), to target acetylcholine (ACh)-mediated crosstalk of cholinergic neurons with cancer and immune cells. Localized BUP-Gel therapy promotes T cell-mediated tumor inhibition and enhances the antitumor response of systemic chemotherapy and immunotherapy. Further, blockade of cancer- and immune cell-specific ACh receptors inhibits tumor growth, alters the TME, and augments the impact of chemotherapy and immunotherapy. Finally, we demonstrate that ACh receptor antagonists polarize macrophages toward an M1-like phenotype and activate T cell immunity in tumor explants of patients. Therefore, targeting cholinergic signals through localized delivery of anesthetics, as well as direct immune reprogramming via cholinergic receptor antagonists, may provide a means to modulate this tripartite crosstalk, with potential implications for therapeutic strategies.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE14333, at NCBI GEO; found in the text, “Cholinergic nerve fibers are associated with…”
Data and code availability
• The raw sequencing data in this study have been deposited in Gene Expression Omnibus (GEO: GSE303917). The remaining data are available within the article and supplemental information. • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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Versions
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Version 2, 28 September 2026
- Authors: added Avinash Bajaj (0000-0002-1333-9316); removed Avinash Bajaj
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 32 authors, 8 keywords, 14 MeSH terms, 6 funders, 80 references, 58 RRIDs.
Cite
This paper
Jain, D., Pandey, N., Jha, S. K., Sinha, S., Singh, R., Alam, J., Aggarwal, B., Chauhan, N., Acharya, A., P.V., A., Dhangar, V., Bhargava, R., Chourasiya, N. K., Khan, A., Sahoo, A. K., Nath, D., Mehra, L., Rana, K., Yadav, P., . . . Bajaj, A. (2026). Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy. Cell reports. Medicine, 7(9), 102994. https://
BibTeX
@article{jain2026targeti
author = {Jain, Dolly and Pandey, Nishant and Jha, Somesh K. and Sinha, Shreya and Singh, Ragini and Alam, Junaid and Aggarwal, Bharti and Chauhan, Neelam and Acharya, Arunima and P.V., Anu and Dhangar, Vandana and Bhargava, Ritika and Chourasiya, Nikhil K. and Khan, Ali and Sahoo, Arnab K. and Nath, Debasish and Mehra, Lalita and Rana, Kajal and Yadav, Poonam and Ralhan, Jahanvi and Rajput, Saroj and Pal, Asish and Maitra, Arindam and Singha, Santiswarup and Panwar, Rajesh and Khurana, Satish and Dasgupta, Ujjaini and Bhoriwal, Sandeep K. and Prabhu, Jyothi S. and Das, Prasenjit and Patil, Veena S. and Bajaj, Avinash},
title = {{Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy}},
journal = {Cell reports. Medicine},
year = {2026},
month = aug,
volume = {7},
number = {9},
pages = {102994},
publisher = {Elsevier},
issn = {2666-3791},
doi = {10.1016/
url = {https://
pmid = {42612638},
pmcid = {PMC13589505}
}
RIS
TY - JOUR
AU - Jain, Dolly
AU - Pandey, Nishant
AU - Jha, Somesh K.
AU - Sinha, Shreya
AU - Singh, Ragini
AU - Alam, Junaid
AU - Aggarwal, Bharti
AU - Chauhan, Neelam
AU - Acharya, Arunima
AU - P.V., Anu
AU - Dhangar, Vandana
AU - Bhargava, Ritika
AU - Chourasiya, Nikhil K.
AU - Khan, Ali
AU - Sahoo, Arnab K.
AU - Nath, Debasish
AU - Mehra, Lalita
AU - Rana, Kajal
AU - Yadav, Poonam
AU - Ralhan, Jahanvi
AU - Rajput, Saroj
AU - Pal, Asish
AU - Maitra, Arindam
AU - Singha, Santiswarup
AU - Panwar, Rajesh
AU - Khurana, Satish
AU - Dasgupta, Ujjaini
AU - Bhoriwal, Sandeep K.
AU - Prabhu, Jyothi S.
AU - Das, Prasenjit
AU - Patil, Veena S.
AU - Bajaj, Avinash
TI - Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy
T2 - Cell reports. Medicine
J2 - Cell Rep Med
PY - 2026
DA - 2026/
VL - 7
IS - 9
SP - 102994
SN - 2666-3791
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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