Insights into tertiary lymphoid structures in the solid tumor microenvironment: anti-tumor mechanism, functional regulation, and immunotherapeutic strategies

Article Figures & Data

Table 1

The immune characteristics of tertiary lymphoid structures in cancers

	Characteristic detecting markers	Subpopulation markers	Prognoses	Reference
B cell zone	CD20⁺B cells	Naïve B cells: CD19⁺CD20⁺IgD⁺	No evaluation	^13,17,18
		Memory B cells: CD19⁺CD20⁺CD27⁺	No evaluation	^13,17,18
		PCs: CD20⁻CD27⁺CD38⁺CD138⁺	Favorable	^13,19,20
		Plasma blasts: CD20⁻CD27⁺ CD38⁺	Favorable	^13,19,20
		FDC: CD21⁺, CD35⁺, CD23⁺, all the markers also expressed on B cells	Favorable	^13,19,20
		Tfh: CD4⁺CXCR5⁺Bcl6⁺	Favorable	^19,20,36
		Tfr: CD4⁺CXCR5⁺foxp3⁺	No evaluation	^68,69
		GC: Bcl-6⁺CD20⁺B cells, or Ki67⁺CD20⁺ B cells	Favorable	^12,13,18
		Breg: IL-10⁺IgA⁺CD19⁺	Unfavorable	^57,58
		Macrophage: CD68⁺	Unfavorable	⁶⁴
T cell zone	CD3⁺T cells, or	Naïve T cell: CCR7⁺CD45RO⁻T cells	No evaluation	¹²
	CD4⁺T cells or	Memory T cells: CD45RO⁺CD45RA⁻T cells	Favorable	¹²
	CD8⁺T cells	Tregs: CD4⁺foxp3⁺T cells	Unfavorable	^13,61
		CTL: CD8⁺ Granzyme B⁺ T cells	Favorable	^12,13,61
		Helper T cells: T-bet⁺Th1	Favorable	^12,15
		GATA3⁺ Th2	Unfavorable	⁶⁴
		RORγt⁺ Th17	No evaluation	⁶⁴
		DC: LAMP3⁺ or CD83⁺ or CD86⁺	Favorable	^12,13
Others:
HEV	PNAd	PNAd or MECA79	Favorable	¹⁷
Chemokines	CXCL13/CXCL12	CCL-2,3,4,5,8,18,19,21; CXCL-9, 10,11,12,13	Favorable	^16,17,18

Table 2

Maturity classifications of tertiary lymphoid structures

	Definition and cellular composition	Marker cell subsets
E-TLS	Dense lymphocytic aggregates without FDCs	CD4⁺ and CD8⁺T cells, CD20⁺B cells, and occasional DCs
PFL-TLS	Having more dense lymphocytic aggregates with FDCs but no GC reaction	CD4⁺ and CD8⁺T cells, CD20⁺B cells, and/or occasional DCs, and FDC
SFL-TLS	Having dense lymphocytic aggregates with FDCs and GC reaction	Bcl6⁺or Ki67⁺CD20⁺B cells, CD38⁺ and/or CD138⁺ CD19⁺B cells