Nonredundant Upregulation of CD112R (PVRIG) and PD-1 on Cytotoxic T Lymphocytes Located in T Cell Nests of Colorectal Cancer
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Nonredundant Upregulation of CD112R (PVRIG) and PD-1 on Cytotoxic T Lymphocytes Located in T Cell Nests of Colorectal Cancer. / Yang, Cheng; Mandelkow, Tim; Bady, Elena; Raedler, Jonas B; Simon, Ronald; Sauter, Guido; Lennartz, Maximilian; Büscheck, Franziska; Luebke, Andreas M; Dum, David; Menz, Anne; Höflmayer, Doris; Weidemann, Sören; Fraune, Christoph; Lebok, Patrick; Uhlig, Ria; Bernreuther, Christian; Jacobsen, Frank; Clauditz, Till S; Wilczak, Waldemar; Minner, Sarah; Burandt, Eike; Steurer, Stefan; Blessin, Niclas C.
in: MODERN PATHOL, Jahrgang 36, Nr. 4, 04.2023, S. 100089.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nonredundant Upregulation of CD112R (PVRIG) and PD-1 on Cytotoxic T Lymphocytes Located in T Cell Nests of Colorectal Cancer
AU - Yang, Cheng
AU - Mandelkow, Tim
AU - Bady, Elena
AU - Raedler, Jonas B
AU - Simon, Ronald
AU - Sauter, Guido
AU - Lennartz, Maximilian
AU - Büscheck, Franziska
AU - Luebke, Andreas M
AU - Dum, David
AU - Menz, Anne
AU - Höflmayer, Doris
AU - Weidemann, Sören
AU - Fraune, Christoph
AU - Lebok, Patrick
AU - Uhlig, Ria
AU - Bernreuther, Christian
AU - Jacobsen, Frank
AU - Clauditz, Till S
AU - Wilczak, Waldemar
AU - Minner, Sarah
AU - Burandt, Eike
AU - Steurer, Stefan
AU - Blessin, Niclas C
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023/4
Y1 - 2023/4
N2 - Focal T lymphocyte aggregates commonly occur in colorectal cancer; however, their biological significance is unknown. To study focal aggregates of T lymphocytes, a deep learning-based framework for automated identification of T cell accumulations (T cell nests) was developed using CD8, PD-1, CD112R, and Ki67 multiplex fluorescence immunohistochemistry. To evaluate the clinical significance of these parameters, a cohort of 523 colorectal cancers with clinical follow-up data was analyzed. Spatial analysis of locally enriched CD8+ T cell density and cell-to-cell contacts identified T cell nests in the tumor microenvironment of colorectal cancer. CD112R and PD-1 expressions on CD8+ T cells located in T cell nests were found to be elevated compared with those on CD8+ T cells in all other tumor compartments (P < .001 each). Although the highest mean CD112R expression on CD8+ T cells was observed at the invasive margin, the PD-1 expression on CD8+ T cells was elevated in the center of the tumor (P < .001 each). Across all tissue compartments, proliferating CD8+ T cells showed higher relative CD112R and PD-1 expressions than those shown by non-proliferating CD8+ T cells (P < .001 each). Integration of all available spatial and immune checkpoint expression parameters revealed a superior predictive performance for overall survival (area under the curve, 0.65; 95% CI, 0.60-0.70) compared with the commonly used CD8+ tumor-infiltrating lymphocyte density (area under the curve, 0.57; 95% CI, 0.53-0.61; P < .001). Cytotoxic T cells with elevated CD112R and PD-1 expression levels are orchestrated in T cell nests of colorectal cancer and predict favorable patient outcomes, and the spatial nonredundancy underlies fundamental differences between both inhibitory immune checkpoints that provide a rationale for dual anti-CD112R/PD-1 immune checkpoint therapy.
AB - Focal T lymphocyte aggregates commonly occur in colorectal cancer; however, their biological significance is unknown. To study focal aggregates of T lymphocytes, a deep learning-based framework for automated identification of T cell accumulations (T cell nests) was developed using CD8, PD-1, CD112R, and Ki67 multiplex fluorescence immunohistochemistry. To evaluate the clinical significance of these parameters, a cohort of 523 colorectal cancers with clinical follow-up data was analyzed. Spatial analysis of locally enriched CD8+ T cell density and cell-to-cell contacts identified T cell nests in the tumor microenvironment of colorectal cancer. CD112R and PD-1 expressions on CD8+ T cells located in T cell nests were found to be elevated compared with those on CD8+ T cells in all other tumor compartments (P < .001 each). Although the highest mean CD112R expression on CD8+ T cells was observed at the invasive margin, the PD-1 expression on CD8+ T cells was elevated in the center of the tumor (P < .001 each). Across all tissue compartments, proliferating CD8+ T cells showed higher relative CD112R and PD-1 expressions than those shown by non-proliferating CD8+ T cells (P < .001 each). Integration of all available spatial and immune checkpoint expression parameters revealed a superior predictive performance for overall survival (area under the curve, 0.65; 95% CI, 0.60-0.70) compared with the commonly used CD8+ tumor-infiltrating lymphocyte density (area under the curve, 0.57; 95% CI, 0.53-0.61; P < .001). Cytotoxic T cells with elevated CD112R and PD-1 expression levels are orchestrated in T cell nests of colorectal cancer and predict favorable patient outcomes, and the spatial nonredundancy underlies fundamental differences between both inhibitory immune checkpoints that provide a rationale for dual anti-CD112R/PD-1 immune checkpoint therapy.
U2 - 10.1016/j.modpat.2022.100089
DO - 10.1016/j.modpat.2022.100089
M3 - SCORING: Journal article
C2 - 36788088
VL - 36
SP - 100089
JO - MODERN PATHOL
JF - MODERN PATHOL
SN - 0893-3952
IS - 4
ER -
