Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer

Lara R Heij; Xiuxiang Tan; Jakob N Kather; Jan M Niehues; Shivan Sivakumar; Nicole Heussen; Gregory van der Kroft; Steven W M Olde Damink; Sven Lang; Merel R Aberle; Tom Luedde; Nadine T Gaisa; Jan Bednarsch; Drolaiz H W Liu; Jack P M Cleutjens; Dominik P Modest; Ulf P Neumann; Georg J Wiltberger

doi:10.3390/jcm10030490

Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer

Lara R Heij^*, Xiuxiang Tan, Jakob N Kather, Jan M Niehues, Shivan Sivakumar, Nicole Heussen, Gregory van der Kroft, Steven W M Olde Damink, Sven Lang, Merel R Aberle, Tom Luedde, Nadine T Gaisa, Jan Bednarsch, Drolaiz H W Liu, Jack P M Cleutjens, Dominik P Modest, Ulf P Neumann, Georg J Wiltberger

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.

Original language	English
Article number	490
Number of pages	11
Journal	Journal of Clinical Medicine
Volume	10
Issue number	3
DOIs	https://doi.org/10.3390/jcm10030490
Publication status	Published - Feb 2021

Keywords

machine learning
nerve fiber density
pancreatic cancer
spatial arrangements
tertiary lymphoid structures
tumor microenvironment
Spatial arrangements
Tumor microenvironment
Pancreatic cancer
Tertiary lymphoid structures
Machine learning
Nerve fiber density

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10.3390/jcm10030490Licence: CC BY

Cite this

Heij, L. R., Tan, X., Kather, J. N., Niehues, J. M., Sivakumar, S., Heussen, N., van der Kroft, G., Damink, S. W. M. O., Lang, S., Aberle, M. R., Luedde, T., Gaisa, N. T., Bednarsch, J., Liu, D. H. W., Cleutjens, J. P. M., Modest, D. P., Neumann, U. P., & Wiltberger, G. J. (2021). Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer. Journal of Clinical Medicine, 10(3), Article 490. https://doi.org/10.3390/jcm10030490

@article{d468f486f21848acad7eecbbbc570218,

title = "Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer",

abstract = "B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.",

keywords = "machine learning, nerve fiber density, pancreatic cancer, spatial arrangements, tertiary lymphoid structures, tumor microenvironment, Spatial arrangements, Tumor microenvironment, Pancreatic cancer, Tertiary lymphoid structures, Machine learning, Nerve fiber density",

author = "Heij, {Lara R} and Xiuxiang Tan and Kather, {Jakob N} and Niehues, {Jan M} and Shivan Sivakumar and Nicole Heussen and {van der Kroft}, Gregory and Damink, {Steven W M Olde} and Sven Lang and Aberle, {Merel R} and Tom Luedde and Gaisa, {Nadine T} and Jan Bednarsch and Liu, {Drolaiz H W} and Cleutjens, {Jack P M} and Modest, {Dominik P} and Neumann, {Ulf P} and Wiltberger, {Georg J}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = feb,

doi = "10.3390/jcm10030490",

language = "English",

volume = "10",

journal = "Journal of Clinical Medicine",

issn = "2077-0383",

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Heij, LR, Tan, X, Kather, JN, Niehues, JM, Sivakumar, S, Heussen, N, van der Kroft, G, Damink, SWMO, Lang, S, Aberle, MR, Luedde, T, Gaisa, NT, Bednarsch, J, Liu, DHW , Cleutjens, JPM, Modest, DP, Neumann, UP & Wiltberger, GJ 2021, 'Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer', Journal of Clinical Medicine, vol. 10, no. 3, 490. https://doi.org/10.3390/jcm10030490

TY - JOUR

T1 - Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer

AU - Heij, Lara R

AU - Tan, Xiuxiang

AU - Kather, Jakob N

AU - Niehues, Jan M

AU - Sivakumar, Shivan

AU - Heussen, Nicole

AU - van der Kroft, Gregory

AU - Damink, Steven W M Olde

AU - Lang, Sven

AU - Aberle, Merel R

AU - Luedde, Tom

AU - Gaisa, Nadine T

AU - Bednarsch, Jan

AU - Liu, Drolaiz H W

AU - Cleutjens, Jack P M

AU - Modest, Dominik P

AU - Neumann, Ulf P

AU - Wiltberger, Georg J

PY - 2021/2

Y1 - 2021/2

N2 - B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.

AB - B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.

KW - machine learning

KW - nerve fiber density

KW - pancreatic cancer

KW - spatial arrangements

KW - tertiary lymphoid structures

KW - tumor microenvironment

KW - Spatial arrangements

KW - Tumor microenvironment

KW - Pancreatic cancer

KW - Tertiary lymphoid structures

KW - Machine learning

KW - Nerve fiber density

U2 - 10.3390/jcm10030490

DO - 10.3390/jcm10030490

M3 - Article

C2 - 33573277

SN - 2077-0383

VL - 10

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

IS - 3

M1 - 490

ER -