Abstract

Over the last decades, significant improvements in reducing the toxicities of allogeneic hematopoietic cell transplantation (allo-HCT) have widened its use as consolidation or salvage therapy for high-risk hematological malignancies. Nevertheless, relapse of the original malignant disease remains an open issue with unsatisfactory salvage options and limited rationales to select among them. In the last years, several studies have highlighted that relapse is often associated with specific genomic and nongenomic mechanisms of immune escape. In this review we summarize the current knowledge about these modalities of immune evasion, focusing on the mechanisms that leverage antigen presentation and pathologic rewiring of the bone marrow microenvironment. We present examples of how this biologic information can be translated into specific approaches to treat relapse, discuss the status of the clinical trials for patients who relapsed after a transplant, and show how dissecting the complex immunobiology of allo-HCT represents a crucial step toward developing new personalized approaches to improve clinical outcomes.

1.
Gooley
TA
,
Chien
JW
,
Pergam
SA
, et al
.
Reduced mortality after allogeneic hematopoietic-cell transplantation
.
N Engl J Med
.
2010
;
363
(
22
):
2091
-
2101
.
2.
Horowitz
M
,
Schreiber
H
,
Elder
A
, et al
.
Epidemiology and biology of relapse after stem cell transplantation
.
Bone Marrow Transplant
.
2018
;
53
(
11
):
1379
-
1389
.
3.
Zeiser
R
,
Vago
L
.
Mechanisms of immune escape after allogeneic hematopoietic cell transplantation
.
Blood
.
2019
;
133
(
12
):
1290
-
1297
.
4.
Christopher
MJ
,
Petti
AA
,
Rettig
MP
, et al
.
Immune escape of relapsed AML cells after allogeneic transplantation
.
N Engl J Med
.
2018
;
379
(
24
):
2330
-
2341
.
5.
Uhl
FM
,
Chen
S
,
O'Sullivan
D
, et al
.
Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans
.
Sci Transl Med
.
2020
;
12
(
567
):
eabb8969
.
6.
Toffalori
C
,
Zito
L
,
Gambacorta
V
, et al
.
Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
.
Nat Med
.
2019
;
25
(
4
):
603
-
611
.
7.
Vago
L
,
Perna
SK
,
Zanussi
M
, et al
.
Loss of mismatched HLA in leukemia after stem-cell transplantation
.
N Engl J Med
.
2009
;
361
(
5
):
478
-
488
.
8.
O’Keefe
C
,
McDevitt
MA
,
Maciejewski
JP
.
Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies
.
Blood
.
2010
;
115
(
14
):
2731
-
2739
.
9.
Crucitti
L
,
Crocchiolo
R
,
Toffalori
C
, et al
.
Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation
.
Leukemia
.
2015
;
29
(
5
):
1143
-
1152
.
10.
Grosso
D
,
Johnson
E
,
Colombe
B
, et al
.
Acquired uniparental disomy in chromosome 6p as a feature of relapse after T-cell replete haploidentical hematopoietic stem cell transplantation using cyclophosphamide tolerization
.
Bone Marrow Transplant
.
2017
;
52
(
4
):
615
-
619
.
11.
McCurdy
SR
,
Iglehart
BS
,
Batista
DA
, et al
.
Loss of the mismatched human leukocyte antigen haplotype in two acute myelogenous leukemia relapses after haploidentical bone marrow transplantation with post-transplantation cyclophosphamide
.
Leukemia
.
2016
;
30
(
10
):
2102
-
2106
.
12.
Villalobos
IB
,
Takahashi
Y
,
Akatsuka
Y
, et al
.
Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation
.
Blood
.
2010
;
115
(
15
):
3158
-
3161
.
13.
Wu
H
,
Shi
J
,
Luo
Y
, et al
.
Assessment of patient-specific human leukocyte antigen genomic loss at relapse after antithymocyte globulin–based T-cell–replete haploidentical hematopoietic stem cell transplant
.
JAMA Netw Open
.
2022
;
5
(
4
):
e226114
.
14.
Toffalori
C
,
Cavattoni
I
,
Deola
S
, et al
.
Genomic loss of patient-specific HLA in acute myeloid leukemia relapse after well-matched unrelated donor HSCT
.
Blood
.
2012
;
119
(
20
):
4813
-
4815
.
15.
Waterhouse
M
,
Pfeifer
D
,
Pantic
M
,
Emmerich
F
,
Bertz
H
,
Finke
J
.
Genome-wide profiling in AML patients relapsing after allogeneic hematopoietic cell transplantation
.
Biol Blood Marrow Transplant
.
2011
;
17
(
10
):
1450
-
1459.e1
.
16.
Jan
M
,
Leventhal
MJ
,
Morgan
EA
, et al
.
Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation
.
Blood Adv
.
2019
;
3
(
14
):
2199
-
2204
.
17.
Mazzi
B
,
Clerici
TD
,
Zanussi
M
, et al
.
Genomic typing for patient-specific human leukocyte antigen-alleles is an efficient tool for relapse detection of high-risk hematopoietic malignancies after stem cell transplantation from alternative donors
.
Leukemia
.
2008
;
22
(
11
):
2119
-
2122
.
18.
Ahci
M
,
Toffalori
C
,
Bouwmans
E
, et al
.
A new tool for rapid and reliable diagnosis of HLA loss relapses after HSCT
.
Blood
.
2017
;
130
(
10
):
1270
-
1273
.
19.
Vago
L
,
Toffalori
C
,
Ahci
M
, et al
.
Incidence of HLA loss in a global multicentric cohort of post-transplantation relapses: results from the Hlaloss Collaborative Study [abstract]
.
Blood
.
2018
;
132
(
suppl 1
):
818
.
20.
Tsirigotis
P
,
Byrne
M
,
Schmid
C
, et al
.
Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT
.
Bone Marrow Transplant
.
2016
;
51
(
11
):
1431
-
1438
.
21.
Vago
L
,
Ciceri
F
.
Choosing the alternative
.
Biol Blood Marrow Transplant
.
2017
;
23
(
11
):
1813
-
1814
.
22.
Ruutu
T
,
de Wreede
LC
,
van Biezen
A
, et al
.
Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT
.
Bone Marrow Transplant
.
2015
;
50
(
12
):
1542
-
1550
.
23.
Christopeit
M
,
Kuss
O
,
Finke
J
, et al
.
Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change
.
J Clin Orthod
.
2013
;
31
(
26
):
3259
-
3271
.
24.
Imus
PH
,
Blackford
AL
,
Bettinotti
M
, et al
.
Major histocompatibility mismatch and donor choice for second allogeneic bone marrow transplantation
.
Biol Blood Marrow Transplant
.
2017
;
23
(
11
):
1887
-
1894
.
25.
Ruggeri
L
,
Capanni
M
,
Urbani
E
, et al
.
Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants
.
Science
.
2002
;
295
(
5562
):
2097
-
2100
.
26.
Vago
L
,
Toffalori
C
,
Ciceri
F
,
Fleischhauer
K
.
Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia
.
Semin Oncol
.
2012
;
39
(
6
):
707
-
715
.
27.
Courtney
AN
,
Tian
G
,
Metelitsa
LS
.
Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy
.
Blood
.
2023
;
141
(
8
):
869
-
876
.
28.
Lepore
M
,
de Lalla
C
,
Gundimeda
SR
, et al
.
A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
.
J Exp Med
.
2014
;
211
(
7
):
1363
-
1377
.
29.
Barros
M
,
de Araújo
ND
,
Magalhães-Gama
F
, et al
.
γδ T cells for leukemia immunotherapy: new and expanding trends
.
Front Immunol
.
2021
;
12
:
729085
.
30.
Shapiro
RM
,
Birch
GC
,
Hu
G
, et al
.
Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse
.
J Clin Invest
.
2022
;
132
(
11
):
e154334
.
31.
Berrien-Elliott
MM
,
Foltz
JA
,
Russler-Germain
DA
, et al
.
Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia
.
Sci Transl Med
.
2022
;
14
(
633
):
eabm1375
.
32.
Wang
CQ
,
Lim
PY
,
Tan
AH-M
.
Gamma/delta T cells as cellular vehicles for anti-tumor immunity
.
Front Immunol
.
2023
;
14
:
1282758
.
33.
Chapuis
AG
,
Egan
DN
,
Bar
M
, et al
.
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant
.
Nat Med
.
2019
;
25
(
7
):
1064
-
1072
.
34.
Rovatti
PE
,
Zito
L
,
Draghi
E
, et al
.
Exploiting an anti-CD3/CD33 bispecific antibody to redirect donor T cells against HLA loss leukemia relapses [abstract]
.
Blood
.
2019
;
134
(
suppl 1
):
513
.
35.
Wu
H
,
Cai
Z
,
Shi
J
,
Luo
Y
,
Huang
H
,
Zhao
Y
.
Blinatumomab for HLA loss relapse after haploidentical hematopoietic stem cell transplantation
.
Am J Cancer Res
.
2021
;
11
(
6
):
3111
-
3122
.
36.
Gaballa
MR
,
Banerjee
P
,
Milton
DR
, et al
.
Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia
.
Blood
.
2022
;
139
(
12
):
1908
-
1919
.
37.
Bednarski
JJ
,
Zimmerman
C
,
Berrien-Elliott
MM
, et al
.
Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant
.
Blood
.
2022
;
139
(
11
):
1670
-
1683
.
38.
Cui
Q
,
Qian
C
,
Xu
N
, et al
.
CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
.
J Hematol Oncol
.
2021
;
14
(
1
):
82
.
39.
Geramita
E
,
Ventura
K
,
Bhise
S
, et al
.
Pilot trial of interferon-γ and donor lymphocyte infusion to treat relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation
.
Transpl Cell Ther
.
2023
;
29
(
2
):
S45
-
S46
.
40.
Zeiser
R
,
Schmid
C
,
Alatrash
G
, et al
.
Siremadlin monotherapy and in combination with donor lymphocyte infusion for patients with acute myeloid leukemia post allogeneic stem cell transplantation who are in complete remission but at high risk for relapse [abstract]
.
Blood
.
2022
;
140
(
suppl 1
):
8944
-
8945
.
41.
Zeiser
R
,
Devillier
R
,
Mico
MC
, et al
.
TIM-3 inhibitor sabatolimab for patients with acute myeloid leukemia (AML) with measurable residual disease (MRD) detected after allogeneic stem cell transplantation (AlloSCT): preliminary findings from the phase Ib/II Stimulus-AML2 Study [abstract]
.
Blood
.
2023
;
142
(
suppl 1
):
59
.
42.
Godfrey
J
,
Liu
H
,
Yu
J
, et al
.
Pembrolizumab for the treatment of disease relapse after allogeneic hematopoietic stem cell transplantation
.
Blood Adv
.
2023
;
7
(
6
):
963
-
970
.
43.
Davids
MS
,
Kim
HT
,
Costello
C
, et al
.
A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation
.
Blood
.
2020
;
135
(
24
):
2182
-
2191
.
44.
Apostolova
P
,
Kreutmair
S
,
Toffalori
C
, et al
.
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-Immune signature correlates with response
.
Br J Haematol
.
2023
;
203
(
2
):
264
-
281
.
45.
Garcia
JS
,
Flamand
Y
,
Penter
L
, et al
.
Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings
.
Blood
.
2023
;
141
(
15
):
1884
-
1888
.
46.
Schroeder
T
,
Stelljes
M
,
Christopeit
M
, et al
.
Treatment of MDS, AML and CMML relapse after allogeneic blood stem cell transplantation with azacitidine, lenalidomide and donor lymphocyte infusions - final results of the Prospective Azalena-Trial (NCT02472691) [abstract]
.
Blood
.
2021
;
138
(
suppl 1
):
411
.
47.
Oran
B
,
de Lima
M
,
Garcia-Manero
G
, et al
.
A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients
.
Blood Adv
.
2020
;
4
(
21
):
5580
-
5588
.
48.
Pagliuca
S
,
Gurnari
C
,
Hercus
C
, et al
.
Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation
.
Nat Commun
.
2023
;
14
(
1
):
3153
.
49.
Meurer
T
,
Crivello
P
,
Metzing
M
, et al
.
Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM
.
Blood
.
2021
;
137
(
7
):
923
-
928
.
50.
Crivello
P
,
Arrieta-Bolaños
E
,
He
M
, et al
.
Impact of the HLA immunopeptidome on survival of leukemia patients after unrelated donor transplantation
.
J Clin Orthod
.
2023
;
41
(
13
):
2416
-
2427
.
51.
Eagle
K
,
Harada
T
,
Kalfon
J
, et al
.
Transcriptional plasticity drives leukemia immune escape
.
Blood Cancer Discov
.
2022
;
3
(
5
):
394
-
409
.
52.
Curnis
F
,
Gasparri
A
,
Sacchi
A
,
Cattaneo
A
,
Magni
F
,
Corti
A
.
Targeted delivery of IFNγ to tumor vessels uncouples antitumor from counterregulatory mechanisms
.
Cancer Res
.
2005
;
65
(
7
):
2906
-
2913
.
53.
Mucci
A
,
Antonarelli
G
,
Caserta
C
, et al
.
Myeloid cell-based delivery of IFN-γ reprograms the leukemia microenvironment and induces anti-tumoral immune responses
.
EMBO Mol Med
.
2021
;
13
(
10
):
e13598
.
54.
Rossari
F
,
Birocchi
F
,
Naldini
L
,
Coltella
N
.
Gene-based delivery of immune-activating cytokines for cancer treatment
.
Trends Mol Med
.
2023
;
29
(
4
):
329
-
342
.
55.
Rimando
JC
,
Chendamarai
E
,
Rettig
MP
, et al
.
Flotetuzumab and other T-cell immunotherapies upregulate MHC class II expression on acute myeloid leukemia cells
.
Blood
.
2023
;
141
(
14
):
1718
-
1723
.
56.
Tanaka
S
,
Miyagi
S
,
Sashida
G
, et al
.
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia
.
Blood
.
2012
;
120
(
5
):
1107
-
1117
.
57.
Fujita
S
,
Honma
D
,
Adachi
N
, et al
.
Dual inhibition of EZH1/2 breaks the quiescence of leukemia stem cells in acute myeloid leukemia
.
Leukemia
.
2018
;
32
(
4
):
855
-
864
.
58.
Gambacorta
V
,
Beretta
S
,
Ciccimarra
M
, et al
.
Integrated multiomic profiling identifies the epigenetic regulator PRC2 as a therapeutic target to counteract leukemia immune escape and relapse
.
Cancer Discov
.
2022
;
12
(
6
):
1449
-
1461
.
59.
Chan
KL
,
Gomez
J
,
Cardinez
C
, et al
.
Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses
.
Cancer Cell
.
2022
;
40
(
10
):
1190
-
1206.e9
.
60.
Ho
JNHG
,
Schmidt
D
,
Lowinus
T
, et al
.
Targeting MDM2 enhances antileukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation
.
Blood
.
2022
;
140
(
10
):
1167
-
1181
.
61.
Langenbach
M
,
Giesler
S
,
Richtsfeld
S
, et al
.
MDM2 inhibition enhances immune checkpoint inhibitor efficacy by increasing IL-15 and MHC class II production
.
Mol Cancer Res
.
2023
;
21
(
8
):
849
-
864
.
62.
Norde
WJ
,
Maas
F
,
Hobo
W
, et al
.
PD-1/PD-L1 interactions contribute to functional T-cell impairment in patients who relapse with cancer after allogeneic stem cell transplantation
.
Cancer Res
.
2011
;
71
(
15
):
5111
-
5122
.
63.
Noviello
M
,
Manfredi
F
,
Ruggiero
E
, et al
.
Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT
.
Nat Commun
.
2019
;
10
(
1
):
1065
.
64.
Zhou
M
,
Sacirbegovic
F
,
Zhao
K
,
Rosenberger
S
,
Shlomchik
WD
.
T cell exhaustion and a failure in antigen presentation drive resistance to the graft-versus-leukemia effect
.
Nat Commun
.
2020
;
11
(
1
):
4227
.
65.
Gournay
V
,
Vallet
N
,
Peux
V
, et al
.
Immune landscape after allo-HSCT: TIGIT- and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse
.
Blood
.
2022
;
140
(
11
):
1305
-
1321
.
66.
Jain
P
,
Tian
X
,
Cordes
S
, et al
.
Over-expression of PD-1 does not predict leukemic relapse after allogeneic stem cell transplantation
.
Biol Blood Marrow Transplant
.
2019
;
25
(
2
):
216
-
222
.
67.
Kong
Y
,
Zhang
J
,
Claxton
DF
, et al
.
PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation
.
Blood Cancer J
.
2015
;
5
(
7
):
e330
.
68.
Hutten
TJA
,
Norde
WJ
,
Woestenenk
R
, et al
.
Increased coexpression of PD-1, TIGIT, and KLRG-1 on tumor-reactive CD8+ T cells during relapse after allogeneic stem cell transplantation
.
Biol Blood Marrow Transplant
.
2018
;
24
(
4
):
666
-
677
.
69.
Williams
P
,
Basu
S
,
Garcia-Manero
G
, et al
.
The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia
.
Cancer
.
2019
;
125
(
9
):
1470
-
1481
.
70.
Bashey
A
,
Medina
B
,
Corringham
S
, et al
.
CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation
.
Blood
.
2009
;
113
(
7
):
1581
-
1588
.
71.
Davids
MS
,
Kim
HT
,
Bachireddy
P
, et al
.
Ipilimumab for patients with relapse after allogeneic transplantation
.
N Engl J Med
.
2016
;
375
(
2
):
143
-
153
.
72.
Gros
F-X
,
Cazaubiel
T
,
Forcade
E
, et al
.
Severe acute GvHD following administration of ipilimumab for early relapse of AML after haploidentical stem cell transplantation
.
Bone Marrow Transplant
.
2017
;
52
(
7
):
1047
-
1048
.
73.
Penter
L
,
Zhang
Y
,
Savell
A
, et al
.
Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation
.
Blood
.
2021
;
137
(
23
):
3212
-
3217
.
74.
Yang
H
,
Bueso-Ramos
C
,
DiNardo
C
, et al
.
Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents
.
Leukemia
.
2014
;
28
(
6
):
1280
-
1288
.
75.
Goodyear
O
,
Agathanggelou
A
,
Novitzky-Basso
I
, et al
.
Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia
.
Blood
.
2010
;
116
(
11
):
1908
-
1918
.
76.
Penter
L
,
Liu
Y
,
Wolff
JO
, et al
.
Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease
.
Blood
.
2023
;
141
(
15
):
1817
-
1830
.
77.
Yared
JA
,
Hardy
N
,
Singh
Z
, et al
.
Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation
.
Bone Marrow Transplant
.
2016
;
51
(
6
):
850
-
852
.
78.
Albring
JC
,
Inselmann
S
,
Sauer
T
, et al
.
PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation
.
Bone Marrow Transplant
.
2017
;
52
(
2
):
317
-
320
.
79.
Abbas
HA
,
Hao
D
,
Tomczak
K
, et al
.
Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy
.
Nat Commun
.
2021
;
12
(
1
):
6071
.
80.
Singh
AK
,
Porrata
LF
,
Aljitawi
O
, et al
.
Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin’s lymphoma
.
Bone Marrow Transplant
.
2016
;
51
(
9
):
1268
-
1270
.
81.
Goswami
M
,
Gui
G
,
Dillon
LW
, et al
.
Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia
.
J Immunother Cancer
.
2022
;
10
(
1
):
e003392
.
82.
Qian
C-S
,
Ma
X
,
Wang
J
, et al
.
PD1 inhibitor in combination with 5-azacytidine and low-dose DLI for the successful treatment of AML patients who relapsed after transplantation
.
Bone Marrow Transplant
.
2021
;
56
(
5
):
1003
-
1005
.
83.
Mishra
SK
,
Millman
SE
,
Zhang
L
.
Metabolism in acute myeloid leukemia: mechanistic insights and therapeutic targets
.
Blood
.
2023
;
141
(
10
):
1119
-
1135
.
84.
Chang
C-H
,
Qiu
J
,
O'Sullivan
D
, et al
.
Metabolic competition in the tumor microenvironment is a driver of cancer progression
.
Cell
.
2015
;
162
(
6
):
1229
-
1241
.
85.
Apostolova
P
,
Pearce
EL
.
Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment
.
Trends Immunol
.
2022
;
43
(
12
):
969
-
977
.
86.
Fischer
K
,
Hoffmann
P
,
Voelkl
S
, et al
.
Inhibitory effect of tumor cell–derived lactic acid on human T cells
.
Blood
.
2007
;
109
(
9
):
3812
-
3819
.
87.
Bergeron
A
,
Chevret
S
,
Granata
A
, et al
.
Effect of azithromycin on airflow decline-free survival after allogeneic hematopoietic stem cell transplant: the ALLOZITHRO Randomized Clinical Trial
.
JAMA
.
2017
;
318
(
6
):
557
-
566
.
88.
Vallet
N
,
Le Grand
S
,
Bondeelle
L
, et al
.
Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation
.
Blood
.
2022
;
140
(
23
):
2500
-
2513
.
89.
Ansari
AW
,
Sharif-Askari
FS
,
Jayakumar
MN
, et al
.
Azithromycin differentially alters TCR-activated helper T cell subset phenotype and effector function
.
Front Immunol
.
2020
;
11
:
556579
.
90.
Vallet
N
,
Salmona
M
,
Malet-Villemagne
J
, et al
.
Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses
.
Cell Host Microbe
.
2023
;
31
(
8
):
1386
-
1403.e6
.
91.
Peled
JU
,
Devlin
SM
,
Staffas
A
, et al
.
Intestinal microbiota and relapse after hematopoietic-cell transplantation
.
J Clin Oncol
.
2017
;
35
(
15
):
1650
-
1659
.
92.
Sari
I
,
Cetin
A
,
Kaynar
L
, et al
.
Disturbance of pro-oxidative/antioxidative balance in allogeneic peripheral blood stem cell transplantation
.
Ann Clin Lab Sci
.
2008
;
38
(
2
):
120
-
125
.
93.
Sabuncuoğlu
S
,
Kuşkonmaz
B
,
Uckun Çetinkaya
D
,
Özgüneş
H
.
Evaluation of oxidative and antioxidative parameters in pediatric hematopoietic SCT patients
.
Bone Marrow Transplant
.
2012
;
47
(
5
):
651
-
656
.
94.
Kong
H
,
Chandel
NS
.
Regulation of redox balance in cancer and T cells
.
J Biol Chem
.
2018
;
293
(
20
):
7499
-
7507
.
95.
Karl
F
,
Liang
C
,
Böttcher-Loschinski
R
, et al
.
Oxidative DNA damage in reconstituting T cells is associated with relapse and inferior survival after allo-SCT
.
Blood
.
2023
;
141
(
13
):
1626
-
1639
.
96.
Munn
DH
,
Sharma
MD
,
Baban
B
, et al
.
GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase
.
Immunity
.
2005
;
22
(
5
):
633
-
642
.
97.
Mussai
F
,
De Santo
C
,
Abu-Dayyeh
I
, et al
.
Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment
.
Blood
.
2013
;
122
(
5
):
749
-
758
.
98.
Serra
S
,
Horenstein
AL
,
Vaisitti
T
, et al
.
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death
.
Blood
.
2011
;
118
(
23
):
6141
-
6152
.
99.
Dulphy
N
,
Henry
G
,
Hemon
P
, et al
.
Contribution of CD39 to the immunosuppressive microenvironment of acute myeloid leukaemia at diagnosis
.
Br J Haematol
.
2014
;
165
(
5
):
722
-
725
.
100.
Staron
MM
,
Gray
SM
,
Marshall
HD
, et al
.
The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8+ T cells during chronic infection
.
Immunity
.
2014
;
41
(
5
):
802
-
814
.
101.
Ho
P-C
,
Liu
P-S
.
Metabolic communication in tumors: a new layer of immunoregulation for immune evasion
.
J Immunother Cancer
.
2016
;
4
:
4
.
102.
Gottschalk
S
,
Anderson
N
,
Hainz
C
,
Eckhardt
SG
,
Serkova
NJ
.
Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells
.
Clin Cancer Res
.
2004
;
10
(
19
):
6661
-
6668
.
103.
Yang
W
,
Bai
Y
,
Xiong
Y
, et al
.
Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
.
Nature
.
2016
;
531
(
7596
):
651
-
655
.
104.
Nayak-Kapoor
A
,
Hao
Z
,
Sadek
R
, et al
.
Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors
.
J Immunother Cancer
.
2018
;
6
:
61
.
You do not currently have access to this content.
Sign in via your Institution