High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

Sehui Kim, Soo Jeong Nam, Changhee Park, Dohee Kwon, Jeemin Yim, Seung Geun Song, Chan Young Ock, Young A. Kim, Sung Hye Park, Tae Min Kim, Yoon Kyung Jeon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+. PD-1+ and CD8+ tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+. The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8+, P=.050; PD-1+, P=.019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8+ and PD-1+ TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P=.026), and those with increased CD8+ or PD-1+ TILs tended to have a better overall survival (P=.081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1+ TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8+ or PD-1+ TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8+ or PD-1+ TILs had the best prognosis. In validation group, increased CD8+ or PD-1+ TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8+ and PD-1+ TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.

Original languageEnglish
Article numbere1626653
JournalOncoImmunology
Volume8
Issue number9
DOIs
StatePublished - 2 Sep 2019

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Tumor-Infiltrating Lymphocytes
Lymphoma, Large B-Cell, Diffuse
Central Nervous System
Survival
Cellular Microenvironment
Neoplasms
Biomarkers

Keywords

  • Primary central nervous system lymphoma
  • diffuse large Bcell lymphoma
  • programmed cell death ligand1
  • programmed cell death1
  • tumorinfiltrating lymphocytes

Cite this

Kim, Sehui ; Nam, Soo Jeong ; Park, Changhee ; Kwon, Dohee ; Yim, Jeemin ; Song, Seung Geun ; Ock, Chan Young ; Kim, Young A. ; Park, Sung Hye ; Kim, Tae Min ; Jeon, Yoon Kyung. / High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system. In: OncoImmunology. 2019 ; Vol. 8, No. 9.
@article{bb83bd40111a401e98811c88d8449418,
title = "High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system",
abstract = "We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30{\%} of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30{\%} of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+. PD-1+ and CD8+ tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7{\%}) were tPD-L1+ and 47 cases (48{\%}) were tmPD-L1+. The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8+, P=.050; PD-1+, P=.019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8+ and PD-1+ TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P=.026), and those with increased CD8+ or PD-1+ TILs tended to have a better overall survival (P=.081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1+ TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8+ or PD-1+ TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8+ or PD-1+ TILs had the best prognosis. In validation group, increased CD8+ or PD-1+ TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8+ and PD-1+ TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.",
keywords = "Primary central nervous system lymphoma, diffuse large Bcell lymphoma, programmed cell death ligand1, programmed cell death1, tumorinfiltrating lymphocytes",
author = "Sehui Kim and Nam, {Soo Jeong} and Changhee Park and Dohee Kwon and Jeemin Yim and Song, {Seung Geun} and Ock, {Chan Young} and Kim, {Young A.} and Park, {Sung Hye} and Kim, {Tae Min} and Jeon, {Yoon Kyung}",
year = "2019",
month = "9",
day = "2",
doi = "10.1080/2162402X.2019.1626653",
language = "English",
volume = "8",
journal = "OncoImmunology",
issn = "2162-4011",
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}

High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system. / Kim, Sehui; Nam, Soo Jeong; Park, Changhee; Kwon, Dohee; Yim, Jeemin; Song, Seung Geun; Ock, Chan Young; Kim, Young A.; Park, Sung Hye; Kim, Tae Min; Jeon, Yoon Kyung.

In: OncoImmunology, Vol. 8, No. 9, e1626653, 02.09.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

AU - Kim, Sehui

AU - Nam, Soo Jeong

AU - Park, Changhee

AU - Kwon, Dohee

AU - Yim, Jeemin

AU - Song, Seung Geun

AU - Ock, Chan Young

AU - Kim, Young A.

AU - Park, Sung Hye

AU - Kim, Tae Min

AU - Jeon, Yoon Kyung

PY - 2019/9/2

Y1 - 2019/9/2

N2 - We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+. PD-1+ and CD8+ tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+. The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8+, P=.050; PD-1+, P=.019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8+ and PD-1+ TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P=.026), and those with increased CD8+ or PD-1+ TILs tended to have a better overall survival (P=.081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1+ TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8+ or PD-1+ TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8+ or PD-1+ TILs had the best prognosis. In validation group, increased CD8+ or PD-1+ TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8+ and PD-1+ TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.

AB - We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+. PD-1+ and CD8+ tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+. The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8+, P=.050; PD-1+, P=.019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8+ and PD-1+ TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P=.026), and those with increased CD8+ or PD-1+ TILs tended to have a better overall survival (P=.081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1+ TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8+ or PD-1+ TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8+ or PD-1+ TILs had the best prognosis. In validation group, increased CD8+ or PD-1+ TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8+ and PD-1+ TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.

KW - Primary central nervous system lymphoma

KW - diffuse large Bcell lymphoma

KW - programmed cell death ligand1

KW - programmed cell death1

KW - tumorinfiltrating lymphocytes

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U2 - 10.1080/2162402X.2019.1626653

DO - 10.1080/2162402X.2019.1626653

M3 - Article

VL - 8

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 9

M1 - e1626653

ER -