Table 4.
Targeting TIL-B cells for immunotherapy.
| Agent | Phase | Description | Related functions |
|---|---|---|---|
| GVAX | Neoadjuvant clinical trial (NCT02451982 and NCT02648282) | Therapeutic cancer vaccine | Induce GM-CSF secretion, promote TLS formation, facilitate TIL infiltration, foster effector T cell activation and cellular communications (206, 207). |
| Anti-VEGFR | Preclinical | Angiogenesis modulator | Used as an adjuvant to enhance ICB therapy, induce HEV formation, improve anti-PD-L1 treatment, promote TIL infiltration (208). |
| GSK3359609 | Phase II/III clinical trial (NCT04128696 and NCT04428333) | ICOS agonist | Promote memory and effector T cell development, induce specific humoral immune responses (209). |
| Engineered DCs | Preclinical Phase I clinical trial (NCT01574222) |
Targeted cytokine/chemokine delivery system | Targeted expression of ideal cytokines or chemokines, initiate TLS resemble, enhance Th1 cell skewing, promote CD8+ CTL infiltration (210–212). |
| CXCL13-coupled CpG-ODN | Preclinical | Therapeutic cancer vaccine | Targeted delivering of stimulatory CpG-ODN to effector B cells, activate effector TIL-B cells while block the generation of Breg cells, promote GrB-expressing CTLs (78). |
| Nanoengineered synthetic immune niches | Preclinical | Synthetic scaffolds with modified TILs and TAA-pulsed DCs | Artificial-designed “TLSs” for reprogramming immunosuppressive TME (213–215). |
| Tirabrutinib | Preclinical | BTK inhibitor | Suppress Breg cell accumulation, reduce IL-10 and IL-35 secretion, foster CD8+ CTL accumulation (68). |
| Cobimetinib | Preclinical | MEK inhibitor | Reduce Breg cell infiltration, interrupt chronic BCR signaling, spare anti-tumor humoral immunity (216). |
| Resveratrol | Preclinical | STAT3 inhibitor | Hamper Breg cell generation, downregulate TGF-β secretion, impair the conversion of FoxP3+ Treg cells (75, 217) |
| Lipoxin A4 | Preclinical | Lipid mediator | Suppress Breg cell induction, reduce Treg cell proliferation, relieve CTL activities (218). |
| IL-35 neutralizing antibody | Preclinical | IL-35 antidote | Reduce PD-L1+ Breg cells, increase CD8+CXCR3+CCR5+ T cells, improve anti-PD-1 treatment, enhance IgG- and IgA- expressing plasma cell differentiation (53, 219, 220). |
TIL-B cell, tumor-infiltrating B cell; GM-CSF: granulocyte-macrophage colony-stimulating factor; VEGFR, vascular endothelial growth factor receptor; ICB, immune checkpoint blockage; TAA, tumor-associated antigen; ICOS, inducible T cell costimulator; DC, dendritic cell; TLS, tertiary lymphoid structure; IL-10, interleukin-10; GrB, granzyme B; MEK, mitogen/extracellular signal-regulated kinase; BCR, B cell receptor; BTK, Bruton’s tyrosine kinase; ODN, oligonucleotide.