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Targeting the Microenvironment in Hodgkin Lymphoma: Opportunities and Challenges

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Part of the Molecular Pathology Library book series (MPLB)

Abstract

The tumor cells in Hodgkin lymphoma (HL) constitute a minority of the affected tissue, while the microenvironment constitutes more than 95% of the total cell population. It has become evident that the infiltrating cells are not just innocent bystanders but active players involved in the pathogenesis of HL. The apparent dependence of the tumor cells on cells present in the microenvironment indicates the potential for therapeutic intervention aiming at targeting specific cell types or factors in the microenvironment. This can be achieved by inhibiting tumor cell-supporting signals or eliminating suppressive factors of the antitumor immune response. In this chapter we will summarize the individual components of the microenvironment, their relevance for tumor cell survival, and possible therapeutic interventions aiming at shifting the balance from a tumor cell-supporting toward a tumor cell-killing microenvironment.

Keywords

Hodgkin lymphoma Microenvironment Immune escape Antitumor immune responses Immune checkpoint Therapy 

Abbreviations

B2M

β2-microglobulin

CC

CC chemokine

CIITA

Class II transactivator

CREBBP

cAMP response element-binding protein-binding protein

CTGF

Connective tissue growth factor

CTLA4

Cytotoxic T-lymphocyte-associated protein 4

CTLs

Cytotoxic T cells

CXC

CXC chemokine

DDR

Discoidin domain receptor tyrosine kinase

DHMEQ

Dehydroxymethylepoxyquinomicin

DLBCL

Diffuse large B-cell lymphoma

EBNA

Epstein-Barr nuclear antigen

EBV

Epstein-Barr virus

EPHB1

Ephrin type-B receptor 1

HDAC

Histone deacetylases

HGF

Hepatocyte growth factor

HL

Classical Hodgkin lymphoma

HLA

Human leukocyte antigen

HRS

Hodgkin and Reed-Sternberg

HSP

Heat shock protein

HuR

Human antigen R

IL

Interleukin

L

Ligand

Lag3

Lymphocyte-activation protein 3

LFA

Lymphocyte function-associated antigen

LMP

Latent membrane protein

LP

Lymphocyte-predominant tumor

LT

Lymphotoxin

MAGE-A4

Melanoma-associated antigen 4

MAPK

Mitogen-activated protein kinase

miR

MicroRNA

NF-κB

Nuclear factor-kappa B

NGF

Nerve growth factor

NIK

NF-κB-inducing kinase

NK

Natural killer

NKG2D

NK cell receptor D

NLPHL

Nodular lymphocyte-predominant Hodgkin lymphoma

NS

Nodular sclerosis

ORR

Objective response rate

PD-1

Programmed cell death protein 1

PDGFRA

Platelet-derived growth factor receptor alpha

PMBCL

Primary mediastinal large B-cell lymphoma

PRAME

Preferentially expressed antigen in melanoma

PTPN1

Protein tyrosine phosphatase, non-receptor type 1

R

Receptor

RON

Recepteur d’origine nantais

RTK

Receptor tyrosine kinases

SOCS

Suppressor of cytokine signaling

SSX2

Synovial sarcoma X

Tfh

T follicular helper

TGF

Transforming growth factor

Th

T helper

TIM3

T-cell immunoglobulin and mucin-domain containing-3

TNF

Tumor necrosis factor

TNFAIP3

TNF alpha-induced protein 3

TNFRSF

Tumor necrosis factor receptor superfamily

Tr-1

T regulatory 1

TRAF

TNF receptor-associated factor

Treg

T regulatory cell

TRK

Tropomyosin receptor kinase

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pathology and Medical BiologyUniversity of Groningen, University Medical Center GroningenGZ GroningenThe Netherlands
  2. 2.Center for Lymphoid Cancer, British Columbia Cancer AgencyVancouverCanada
  3. 3.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada

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