Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy
Valind, Anders LU
; Verhoeven, Bronte Manouk
; Enoksson, Jens
LU
; Karlsson, Jenny
LU
; Christensson, Gustav
LU
; Mañas, Adriana
LU
; Aaltonen, Kristina
LU
; Jansson, Caroline
LU
; Bexell, Daniel
LU
and Baryawno, Ninib
, et al.
(2023)
In OncoImmunology
12(1).
- Abstract
Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed. To understand the adaptation of neuroblastoma under therapy, we analyzed the transcriptomic landscape in 46 clinical tumor samples collected before (PRE) or after (POST) treatment from 22 neuroblastoma patients. RNA sequencing revealed that many of the top-upregulated biological processes in POST
MYCN amplified (MNA
+) tumors compared... (More)Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed. To understand the adaptation of neuroblastoma under therapy, we analyzed the transcriptomic landscape in 46 clinical tumor samples collected before (PRE) or after (POST) treatment from 22 neuroblastoma patients. RNA sequencing revealed that many of the top-upregulated biological processes in POST
(Less)
MYCN amplified (MNA
+) tumors compared to PRE MNA
+ tumors were immune-related, and there was a significant increase in numerous genes associated with macrophages. The infiltration of macrophages was corroborated by immunohistochemistry and spatial digital protein profiling. Moreover, POST MNA
+ tumor cells were more immunogenic compared to PRE MNA
+ tumor cells. To find support for the macrophage-induced outgrowth of certain subpopulations of immunogenic tumor cells following treatment, we examined the genetic landscape in multiple clinical PRE and POST tumor samples from nine neuroblastoma patients revealing a significant correlation between an increased amount of copy number aberrations (CNA) and macrophage infiltration in POST MNA
+ tumor samples. Using an
in vivo neuroblastoma patient-derived xenograft (PDX) chemotherapy model, we further show that inhibition of macrophage recruitment with anti-CSF1R treatment prevents the regrowth of MNA
+ tumors following chemotherapy. Taken together, our work supports a therapeutic strategy for fighting the relapse of MNA
+ neuroblastoma by targeting the immune microenvironment.
- author
- Valind, Anders
LU
; Verhoeven, Bronte Manouk
; Enoksson, Jens
LU
; Karlsson, Jenny
LU
; Christensson, Gustav
LU
; Mañas, Adriana
LU
; Aaltonen, Kristina
LU
; Jansson, Caroline
LU
; Bexell, Daniel
LU
and Baryawno, Ninib
, et al. (More)
- Valind, Anders
LU
; Verhoeven, Bronte Manouk
; Enoksson, Jens
LU
; Karlsson, Jenny
LU
; Christensson, Gustav
LU
; Mañas, Adriana
LU
; Aaltonen, Kristina
LU
; Jansson, Caroline
LU
; Bexell, Daniel
LU
; Baryawno, Ninib
; Gisselsson, David
LU
and Hagerling, Catharina
LU
(Less)
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Child, Animals, Humans, N-Myc Proto-Oncogene Protein, Neoplasm Recurrence, Local, Neuroblastoma, Disease Models, Animal, Macrophages, Tumor Microenvironment
- in
- OncoImmunology
- volume
- 12
- issue
- 1
- article number
- 2184130
- publisher
- Landes Bioscience
- external identifiers
-
- scopus:85149358572
- pmid:36875552
- ISSN
- 2162-4011
- DOI
- 10.1080/2162402X.2023.2184130
- language
- English
- LU publication?
- yes
- id
- 3ca71b2a-2dcf-471a-b8e1-b2899593f94c
- date added to LUP
- 2023-04-03 16:15:58
- date last changed
- 2024-06-13 14:47:43
@article{3ca71b2a-2dcf-471a-b8e1-b2899593f94c,
abstract = {{<p>Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed. To understand the adaptation of neuroblastoma under therapy, we analyzed the transcriptomic landscape in 46 clinical tumor samples collected before (PRE) or after (POST) treatment from 22 neuroblastoma patients. RNA sequencing revealed that many of the top-upregulated biological processes in POST <br>
MYCN amplified (MNA<br>
+) tumors compared to PRE MNA<br>
+ tumors were immune-related, and there was a significant increase in numerous genes associated with macrophages. The infiltration of macrophages was corroborated by immunohistochemistry and spatial digital protein profiling. Moreover, POST MNA<br>
+ tumor cells were more immunogenic compared to PRE MNA<br>
+ tumor cells. To find support for the macrophage-induced outgrowth of certain subpopulations of immunogenic tumor cells following treatment, we examined the genetic landscape in multiple clinical PRE and POST tumor samples from nine neuroblastoma patients revealing a significant correlation between an increased amount of copy number aberrations (CNA) and macrophage infiltration in POST MNA<br>
+ tumor samples. Using an <br>
in vivo neuroblastoma patient-derived xenograft (PDX) chemotherapy model, we further show that inhibition of macrophage recruitment with anti-CSF1R treatment prevents the regrowth of MNA <br>
+ tumors following chemotherapy. Taken together, our work supports a therapeutic strategy for fighting the relapse of MNA<br>
+ neuroblastoma by targeting the immune microenvironment.<br>
</p>}},
author = {{Valind, Anders and Verhoeven, Bronte Manouk and Enoksson, Jens and Karlsson, Jenny and Christensson, Gustav and Mañas, Adriana and Aaltonen, Kristina and Jansson, Caroline and Bexell, Daniel and Baryawno, Ninib and Gisselsson, David and Hagerling, Catharina}},
issn = {{2162-4011}},
keywords = {{Child; Animals; Humans; N-Myc Proto-Oncogene Protein; Neoplasm Recurrence, Local; Neuroblastoma; Disease Models, Animal; Macrophages; Tumor Microenvironment}},
language = {{eng}},
number = {{1}},
publisher = {{Landes Bioscience}},
series = {{OncoImmunology}},
title = {{Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy}},
url = {{http://dx.doi.org/10.1080/2162402X.2023.2184130}},
doi = {{10.1080/2162402X.2023.2184130}},
volume = {{12}},
year = {{2023}},
}