. 2020 Nov 2;18(4):842–859. doi: 10.1038/s41423-020-00565-9

Table. 1.

Phenotype and functional properties of tumor infiltrating lymphocytes.

	Phenotype	Functional properties
T cells
TCRγδ⁺	Express NK-cell markers such as NKG2D. Two main subsets; Vδ1 γδ T cells and Vγ9Vδ2 T cells.	Display both innate and adaptive immune features and are described to exhibit both effector like and regulatory like functions.
TCRαβ⁺ CD4⁺ CD8⁺ Double positive T cells	Effector memory-like phenotype Four main subpopulations: CD4^highCD8^low, CD4^highCD8^high, CD4^medCD8^high, CD4^lowCD8^high.	Cytokine production, expression of inhibitory receptors (PD1, TIM3, TIGIT) and activation markers (HLA-DR, CD38, 4-1BB, Ki67).
TCRαβ⁺ CD4⁻ CD8⁻Double negative T cells	Regulatory-like and/or effector memory-like phenotype.	Different functional properties which might reflect differences between circulating double-negative T cells from healthy donors versus tumor infiltrated double-negative T cells.
CD3⁺ T cell Memory subsets
Stem cell-like memory (TSCM)	CD45RO⁻CD45RA⁺CCR7⁺CD62L⁺CD27⁺CD28⁺ IL7Rα⁺CD95⁺IL2Rβ⁺	Self-renewal, high proliferative capacity, circulation through lymphoid organs, cytokine production.
Central memory (TCM)	CD45RA⁻CD45RO⁺CCR7⁺CD62L⁺ Diverse CD27CD28 expression.	Reduced self-renewal and multipotentcy compared to TSCM. Circulation through lymphoid organs. Limited effector functions.
Effector memory (TEM)	CD45RA⁻CD45RO⁺CCR7⁻CD62L-. Diverse CD27CD28 expression.	Exhibit proinflammatory effector functions. Preferentially traffic through peripheral tissue.
effector memory RA⁺ (TEMRA)	CD45RA⁺CCR7⁻CD27⁻CD28⁻	Terminally differentiated effector T cell. Exhibit cytolytic capacity.
CD8⁺ TCRαβ subsets—Cytotoxic T lymphocytes (CTL)
Tissue-resident memory (TRM)	CD103⁺CD39⁺	Cancer-specific CTL that reside in the tumor epithelium. Often coexpress inhibitory receptors such as PD-1.
Bystander	CD103⁺CD39⁻	Non-cancer-specific CTL that reside in the tumor epithelium. Capable of inducing antitumor immune response.
Progenitor stem-like exhausted (T_PE)	TCF1⁺Slamf6⁺CXCR5⁺PD1⁺ CD39⁻ CX3CR1⁻	Maintain antigen-specific immune response, persist long-term, self-renewal, differentiation into T_EX.
Exhausted (T_EX)	CX3CR1⁺ CD39⁺PD1⁺Tim3⁺ TCF1⁻CXCR5⁻	Exhibit high cytolytic and cytotoxic function.
CD4⁺ TCRαβ⁺
Helper (T_HC)	STAT activated	Direct lysis of tumor cells, inducing CD8⁺ T cells activation and expansion. Improvement the antigen-presenting capacity of dendritic cells
Follicular helper (T_FH)	CXCR5, BCL-6 expression	Promoting B cell activation, expansion, and differentiation into plasma cells. CXCL13 production.
Regulatory (Treg)	FOXP3⁺CD25⁺	Production of suppressive cytokines, modification of antigen-presenting cells, nutrient deprivation, IL-2 exhaustion, and cytolysis.
B cells	CD19⁺CD20⁺
Antigen-presenting	MHC-mediated	Antigen presentation to T cells
Plasma cells (PC)	CD20⁻CD38⁺CD138⁺CD79a⁺	Production of antibodies
Regulatory (Breg)	Lack of phenotypic markers	Production of suppressive cytokines IL-10, IL-35, and TGFβ.
Germinal center	Bcl-6⁺, activation-induced deaminase (AID⁺), Ki67 expression	Enables recombinant class switching of the constant region from IgM/IgD to IgG, IgE, or IgA, and somatic hypermutation of the BCR resulting in increased antigen affinity.
Class-switched	IgG, IgA, or IgE	Contain affinity-matured antibodies; give rise to a highly advanced immune response.
Innate lymphoid cells
Natural killer cells (NK)	CD16⁺NKp30⁺NK46⁺NKp44⁺NKG2D⁺NKG2A⁺	Proinflammatory; high cytolytic capacity; release of granzymes, perforins, and IFNγ production.
Helper-like innate lymphoid cells (ILC)
ILC group 1 (ILC1)	NK1.1⁺ and NKp46⁺	NK-like cells. Production of IFNγ.
ILC group 2 (ILC2)	IL33 receptor ST and CD127⁺	GATA3-dependent function. Proinflammatory.
ILC group 3 (ILC3)	RORγt⁺CD127⁺	Controversial role; both proinflammatory and immune regulatory.