PMID- 38481730
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240315
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Print)
IS  - 2162-4011 (Linking)
VI  - 13
IP  - 1
DP  - 2024
TI  - Prognostic impact of the bone marrow tumor microenvironment, HLA-I and HLA-Ib 
      expression in MDS and CMML progression to sAML.
PG  - 2323212
LID - 10.1080/2162402X.2024.2323212 [doi]
LID - 2323212
AB  - Genetic aberrations and immune escape are fundamental in MDS and CMML initiation 
      and progression to sAML. Therefore, quantitative and spatial immune cell 
      organization, expression of immune checkpoints (ICP), classical human leukocyte 
      antigen class I (HLA-I) and the non-classical HLA-Ib antigens were analyzed in 
      274 neoplastic and 50 non-neoplastic bone marrow (BM) biopsies using conventional 
      and multiplex immunohistochemistry and correlated to publicly available dataset. 
      Higher numbers of tissue infiltrating lymphocytes (TILs) were found in MDS/CMML 
      (8.8%) compared to sAML (7.5%) and non-neoplastic BM (5.3%). Higher T cell 
      abundance, including the CD8(+) T cell subset, inversely correlated with the 
      number of pathogenic mutations and was associated with blast BM counts, ICP 
      expression, spatial T cell distribution and improved patients' survival in MDS 
      and CMML. In MDS/CMML, higher PD-1/PD-L1/PD-L2 and HLA-I, but lower HLA-G 
      expression correlated with a significantly better patients' outcome. Moreover, a 
      closer spatial proximity of T cell subpopulations and their proximity to myeloid 
      blasts showed a stronger prognostic impact when compared to TIL numbers. In sAML 
      - the continuum of MDS and CMML - the number of TILs had no impact on prognosis, 
      but higher CD28 and HLA-I expression correlated with a better outcome of sAML 
      patients. This study underlines the independent prognostic value of the tumor 
      microenvironment in MDS/CMML progression to sAML, which shows the most pronounced 
      immune escape. Moreover, new prognostic markers, like HLA-G expression and 
      spatial T cell distribution, were described for the first time, which might also 
      serve as therapeutic targets.
CI  - (c) 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Bauer, Marcus
AU  - Bauer M
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Jakel, Nadja
AU  - Jakel N
AD  - Department of Hematology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Wilfer, Andreas
AU  - Wilfer A
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
AD  - Krukenberg Cancer Center Halle, University Hospital Halle, Martin Luther 
      University Halle-Wittenberg, Halle, Germany.
FAU - Haak, Anja
AU  - Haak A
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Eszlinger, Markus
AU  - Eszlinger M
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Kelemen, Katalin
AU  - Kelemen K
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Haemmerle, Monika
AU  - Haemmerle M
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
FAU - Al-Ali, Haifa Kathrin
AU  - Al-Ali HK
AD  - Department of Hematology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
AD  - Krukenberg Cancer Center Halle, University Hospital Halle, Martin Luther 
      University Halle-Wittenberg, Halle, Germany.
FAU - Seliger, Barbara
AU  - Seliger B
AD  - Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, Germany.
AD  - Medical Faculty, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, 
      Germany.
AD  - Institute of Translational Immunology, Medical School "Theodor Fontane", 
      Brandenburg an der Havel, Germany.
FAU - Wickenhauser, Claudia
AU  - Wickenhauser C
AD  - Institute of Pathology, University Hospital Halle, Martin Luther University 
      Halle-Wittenberg, Halle, Germany.
LA  - eng
PT  - Journal Article
DEP - 20240306
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (HLA-G Antigens)
SB  - IM
MH  - Humans
MH  - Prognosis
MH  - *HLA-G Antigens/metabolism
MH  - *Bone Marrow/metabolism
MH  - Tumor Microenvironment/genetics
MH  - CD8-Positive T-Lymphocytes
PMC - PMC10936680
OTO - NOTNLM
OT  - HLA-G
OT  - HLA-I
OT  - TILs
OT  - immune escape
OT  - myeloid neoplasm
OT  - spatial immune cell organization
OT  - tumor microenvironment
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2024/03/14 06:46
MHDA- 2024/03/15 06:44
PMCR- 2024/03/06
CRDT- 2024/03/14 04:13
PHST- 2024/03/15 06:44 [medline]
PHST- 2024/03/14 06:46 [pubmed]
PHST- 2024/03/14 04:13 [entrez]
PHST- 2024/03/06 00:00 [pmc-release]
AID - 2323212 [pii]
AID - 10.1080/2162402X.2024.2323212 [doi]
PST - epublish
SO  - Oncoimmunology. 2024 Mar 6;13(1):2323212. doi: 10.1080/2162402X.2024.2323212. 
      eCollection 2024.