Table 2 TLSs in diseases: detection, markers, components, location, prognostic value, and therapeutic effects

From: Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances

Disease

 

Detection

Markers

Components

Location

Prognostic Value

Therapeutic Effects

Ref

Tumor

HNSCC

scRNA-seq

NA

TIL-B cell with GCs

TLSs with GCs

NA

Positive

NA

16

HNSCC

IHC

LAMP3

CCL2

CCL3

CCL4

CCL5

CCL18

CCL19

CCL21

CXCL9

CXCL10

CXCL11

CXCK13

CXCR4

Memory B cells

Immature and activated B cells

memory and activated CD4 + T CD8 + T cells

activated dendritic cells

type I T helper cells MDSC

Intra-tumor

Positive

NA

380

HNSCC

IF

FC

CD3

CD8

FoxP3

CD20

cytokeratin

Cytotoxic

CD4+ T helper cells

Regulatory T cells (Tregs)

B lymphocytes

NA

Positive

PD-L1 positive

484

HNSCC

scRNA-Seq

CXCR3

CCR7

CCR6

CXCR5

CCR1

NA

-

Positive

ICB positive

368

TSCC

IHC

IL10

CD19

Foxp3

CD4

Bregs

Tregs

 

Negative

NA

563

Ovarian Cancer

IF

IHC

RtPCR

ELISA

Western Blot

CD20

CD4

SCD1

CD8α

CXCL13

CCL21

VEGFC

CD4 T cell

CD20 B cell

NA

Positive

PD-1 positive

376

HGSOC

MCPcounter

NA

TLS

NA

Positive

NA

401

HGSOC

IHC

RNA ISH double staining

CXCL13

CD4 T cell

NA

Positive

NA

254

ESCC

H&E

CD20

Ki67

CD21

CD4

LAMP3

CD8

GC

NA

Positive

NA

152

ESCC

mIHC

H&E

CD21

CD23

PD-1

CD1c

CD4

CD8

CD19

CD21

CD138

TLSs

peri-tumor

Positive

PD-1 positive

383

LUAD

H&E

NA

TLSs

NA

Positive

NA

369

LUAD

IHC

CD8

Foxp3

CD20

CD4

DC-Lamp

CCL19

CCL21

CCR7

DC

TLS

NA

Positive

NA

399

LSCC

H&E

IHC

IF

CD21

CD23

CXCL13

GC

TLS

NA

Positive

Neoadjuvant treatment negative

5

NSCLC

H&E

IHC

CD3

CD20

CD21

FDC

T cell

B cell

NA

NA

Neoadjuvant treatment positive

397

NSCLC

scRNA-seq

CD79A

CD83

CD69

SELL

BANK1

HMGA1

AICDA

RGS13

GC

Follicular B cells

Plasma cells

NA

Positive

ICB Positive

397

NSCLC

FC

ELISA

CD14

CD38

CD138

CD27

GC

Memory B cell

NA

Positive

Neoadjuvant treatment positive

59

nmCRC

IHC

H&E

CD20

CD3

CD21

CXCL13

HEV

B cell

T cell

FDCs

GC

HEV

peri-tumor

Positive

NA

384

nmCRC

mIF

CD21

CD23

CXCL13

GC

FDC

NA

Positive

NA

404

CRC

IHC

CD3

CD8

GKA-DR

CD31

MECA-79

CD3 T cell

CD8 T cell

M1 macrophages

Vessels

HEV

Peri-tumor

HEV/TLS

Positive

NA

316

HCC

Pathological examination

Gene expression profiling

CCL2

CCL4

CCL5

CCL8

CCL18

CCL19

CCL21

CXCL9

CXCL10

CXCL11

CXCL13

TLS

Intra-tumor

Positive

NA

19

HCC

H&E

NA

TLSs

Peri-tumor

Negative

NA

385

HCC

FFPE

NA

TLSs

Intra-tumor

Positive

NA

406

CCA

H&E

mIHC

CD20

CD21

TLSs

Intra-tumor

Positive

NA

407

CCA

mIHC

H&E

CD20

CD3

MECA-79

CD21

CD23

TCL1A

PAX5

TNFRSF13C

CD79A

TLSs

Intra-tumor

Positive

NA

386

CCA

mIHC

H&E

CD20

CD3

MECA-79

CD21

CD23

TCL1A

PAX5

TNFRSF13C

CD79A

TLSs

Peri-tumor

Negative

NA

386

iCCA

mIHC

H&E

CD3

CD8

CD20

CD68

CK19

PDL1

CD4

Foxp3

Bcl6

TLSs

Intra-tumor

Positive

NA

382

iCCA

mIHC

H&E

CD3

CD8

CD20

CD68

CK19

PDL1

CD4

Foxp3

Bcl6

TLSs

Peri-tumor

Negative

NA

382

iCCA

mIF

IHC

MECA-79

CD8

CD20

TLSs

NA

Positive

NA

410

cHCC-CCA

Spatial transcriptome sequencing

RNA-seq

IMC

IHC

mIF

CK19

HepPar-1

GPC3

TLSs

Intra-tumor

Positive

NA

564

ccRCC

IHC

CD3

Bcl6

CD8

CD10

Foxp3

TLSs

NA

Negative

Negative

377

ccRCC

IHC

H&E

CD3

CD20

CD21

CD23

TLSs

Tumor-proximal

Positive

NA

412

ccRCC

IHC

H&E

CD3

CD20

CD21

CD23

TLSs

Tumor-distal

Negative

NA

412

ccRCC

IHC

CD3

CD8a

CD20

CD4

CD68

CD31

Pan-Keratin

Ecad

αSMA

VIM

T cells

B cells

Macrophages

tumor cells

epithelial cells

endothelial cells

fibroblasts

NA

Positive

NA

135

BCa

Pathological examination

CXCL13

NA

NA

ICB positive

NA

256

BCa

TCGA

NA

TLSs

NA

Negative

ICB negative

413

MIBC

TCGA

NA

TLSs

NA

Positive

ICB positive

414

UCB

IHC

CD20

CD3

Bcl-6

CD21

TLSs

GC

NA

Positive

NA

288

EVaGC

mIHC

CD20

CD21

CD4

CD8

Foxp3

TLSs

Intra-tumor

Positive

NA

417

GC

mIHC

MECA-79

CD21

FDC

HEV

NA

Positive

NA

418

Bladder Cancer

scRNA-seq

NA

TLSs

NA

Positive

NA

366

Bladder Cancer

TCGA

NA

TLSs

NA

Positive

NA

420

Bladder Cancer

IHC

CD4

CD8

CD163

Foxp3

TLSs

Peri-tumor

Negative

NA

387

TNBC

H&E

IHC

CD8

CD45

CD20

Cytotoxic T cells

Memory T cells

B cells

NA

Positive

NA

421

Breast Cancers

IHC

CD3

CD20

CD23

T cell

B cell

FDC

NA

Positive

NA

422

EC

TCGA

NA

TLSs

NA

Positive

NA

424

EC

IHC

CD8

CD20

CD4

CD38

CD23

TLSs

Intra-tumor

Positive

NA

425

Glioma

TCGA

NA

TLSs

NA

Positive

NA

381

Melanoma

mIHC

CD8

CD20

KIT67

CD4

TLSs

NA

Positive

NA

388

Melanoma

scRNA-Seq

IHC

CD20

CD40

CD20CD22ADAM28 B cell

NA

NA

ICB positive

565

ePM

IHC

scRNA-Seq

NA

TLSs

NA

Positive

NA

431

EMPM

FFPE

NA

TLSs

NA

NA

Positive

432

PDAC

scRNA-seq

mIHC

FC

CD3

CD21

CD103

CD8

CD20

PNAd

BCL6

Ki67

CD8 T cell

IgG1 class-switched memory B cell

Memory CD4 T cell

Naive B cell

NK cell

GC

NA

Positive

NA

77

PDAC

scRNA-Seq

mIF

NA

TLSs

NA

Positive

Chemotherapy positive

277

PDAC

H&E

mIHC

CD4

CD8

CD20

CD11c

CD15

CD68

Foxp3

CD4T cells

CD8T cells

B cells

DCs

Granulocytes

Treg

Macrophages

NA

Positive

NA

427

PDAC

IHC

CD4

CD8

CD20

CD45

CD68

Foxp3

TLSs

NA

Positive

NA

428

cSCC

IHC

H&E

CD3

CD8

CD 21

MECA-79

B cells

T cells

HEV

FDC

NA

Positive

NA

379

MCC

IHC

RNA-seq

CD3

CD8

CD20

CD21

T cells

B cells

NA

Positive

NA

430

Autoimmune disease

SLE

LN

IHC

NA

TLSs

NA

NA

NA

196

SLE

LN

IHC

CD20

CD3

CD21

B cells

T cells

FDC

Kidney

Negative

NA

439

SS

FC

RNA-seq

NKp30

CD337

NCR3

Salivary glands

NA

NA

182

SS

ELISA

RT-PCR

CX3CL1

CX3CL1

Salivary glands

NA

NA

267

RA

IHC

IF

CD3

CD20

CD138

CD68

MC

B cells

Synovial tissue

Negative

NA

436

MS

FC

RNA-seq

NA

TLSs

Meninges

NA

NA

443

MS

IHC

IF

PCR

CD4

CD8

CD79a

IBA1

CD68

TLSs

NA

NA

NA

445

Uveitis

IHC

CD3

CD20

CD21

B cells

T cells

FDC

Retina

NA

NA

291

Uveitis

scRNA-seq

NA

TLSs

Retina

NA

NA

448

GCA

IHC

IF

CD3

CD20

CD21

CD68

CD138

T cells

B cells

FDC

Macrophages

Plasma cells

Aortic

NA

NA

450

GCA

IHC

PCR

IF

CD3

CD20

CD21

T cells

B cells

FDC

Temporal artery

NA

NA

51

Pemphigus

IHC

CD3

CD20

CD138

T cells

B cells

Plasma cells

NA

NA

NA

292

Pemphigus

IHC

RNA-seq

CD4

CXCL13

Tregs

Memory T cells

NA

NA

NA

137

Transplant

Heart transplant

IHC

CD3

CD45

MECA -79

T cells

B cells

PNAd

Heart

Negative

NA

455

Heart transplant

IHC

CD20

CD27

TLSs

Epicardial coronary arteries

Negative

NA

62

Kidney transplant

IHC

H&E

CD20

TLSs

Kidney

NA

NA

457

Kidney transplant

IHC

CD20

TLSs

Kidney

Positive

NA

456

Lung transplant

IHC

H&E

NA

TLSs

Lung

Positive

NA

458

Infection

Colitis

IF

B220

MHCII

CD11c-

CD3

CD11c

MHCII+

CD35

CD31

MAdCAM-1

B cells

T cells

DC

FDC

Vessel

HEV

Colon

No effect

NA

459

Crohn’s disease (CD)

IF

CD20

CD3

IL-33R

CD138

PNAd

B cells

T cells

innate lymphoid cells

plasma cells

Lymphatic vessels

NA

NA

370

CD

IHC

CD20

CD3

CD31

gp38

PNAd

CD21

CD19

B cells

T cells

Vessel

Lymphatic vessels

HEV

FDC

Transmural lesions

Negative

NA

460

COPD

IHC

CD19

TLSs

SIgA- airway

Negative

NA

179

COPD

IHC

CD20

CD21

B cells

FDC

Distal lung tissue (peribronchiolar and parenchymal)

No relation

NA

461

COPD

IHC

IL-18

CD68

GC

NA

Negative

NA

462

Chronic rhinosinusitis with nasal polyps (CRSwNP)

IHC/IF

CD3

CD20

CD21

Ki-67

PNAd

D2-40

CD11c

CD138

CD68

CD56

T cells

B cells

FDC

Proliferating B cells

HEV

Lymphatic vessels

DC

Plasma cells

Macrophages

NK cells

NA

Negative

NA

464

Tuberculosis (TB)

IHC

B22

CD3

B cells

T cells

NA

Positive

NA

466

Influenza virus infection

IHC

PNA staining

B220

CD11c

CD4

CD8

M2

CD138

GL-7

B cells

DC

T cells

FDC

Plasma cells

GC

Bronchi

Lung interstitium

Positive

NA

177

Influenza virus infection

HE

IHC/IF

B220

CD3

CD11c

GL7

B cells

T cells

DC

GC

Bronchi

Positive

NA

197

Staphylococcus aureus lung infection

IHC

CD20

CD3

PNAd

CD21

PCNA

B cells

T cells

HEV

FDC

GC

Bronchi

No relation

NA

467

Viral

Myocarditis

(VMC)

HE

IHC/IF

CD3

B220

CD21

Ki67

PNAd

T cells

B cells

FDC

HEV

NA

Negative

NA

469