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Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients

Lokhande, Lavanya LU ; Nilsson, Daniel LU ; de Matos Rodrigues, Joana LU ; Hassan, May LU ; Olsson, Lina M LU ; Pyl, Paul-Theodor LU ; Vasquez, Louella LU ; Porwit, Anna LU ; Gerdtsson, Anna Sandström LU and Jerkeman, Mats LU , et al. (2024) In Cancers 16(13).
Abstract

With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a... (More)

With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
16
issue
13
publisher
MDPI AG
external identifiers
  • scopus:85198391257
  • pmid:39001353
ISSN
2072-6694
DOI
10.3390/cancers16132289
language
English
LU publication?
yes
id
a274011a-9dfd-4bb3-b812-5f26d4916673
date added to LUP
2024-09-18 09:30:31
date last changed
2025-07-11 08:10:45
@article{a274011a-9dfd-4bb3-b812-5f26d4916673,
  abstract     = {{<p>With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.</p>}},
  author       = {{Lokhande, Lavanya and Nilsson, Daniel and de Matos Rodrigues, Joana and Hassan, May and Olsson, Lina M and Pyl, Paul-Theodor and Vasquez, Louella and Porwit, Anna and Gerdtsson, Anna Sandström and Jerkeman, Mats and Ek, Sara}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{13}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients}},
  url          = {{http://dx.doi.org/10.3390/cancers16132289}},
  doi          = {{10.3390/cancers16132289}},
  volume       = {{16}},
  year         = {{2024}},
}