CD8+ T cells

Byaibio

CD8+ T cells are cytotoxic effector T cells central to antitumor immunity, and in several tumor settings their infiltration, activation, and interaction with antigen-presenting cells are limiting steps. In KRAS-mutated biliary tract cancer, these cells show reduced infiltration and impaired APC interactions, consistent with a dysfunctional tumor-immune interface (PMID:41186264). They are also implicated in response to immunotherapies such as agonistic CD40 antibody therapy in pancreatic ductal adenocarcinoma, anti-PD-1 combinations, and ipilimumab-driven priming, where their activity can be partially or robustly required (PMID:41935073, PMID:41998161, PMID:41989053). Recent studies also highlight specialized states, including brain-resident memory CD8+ T cells that mediate durable protection against intracranial malignancy and liver-depleted virus-specific/tumor-specific CD8 T cells after Fc-intact anti-PD-1 therapy (PMID:41983390, PMID:41950082). Mechanistically, altered lipid metabolism and glycocholic acid can suppress CD8+ T-cell function, whereas interventions such as cryoablation, DDR1 knockout, STING agonist delivery, and inhalable chemoimmunotherapy can expand or recruit these cells into tumors (PMID:41946907, PMID:41935049, PMID:41962054, PMID:41955504, PMID:41947504).

Tumor immunity and immunotherapy

  • CD8+ T cells are key effector cells in antitumor immunity and were partially required for the efficacy of agonistic CD40 antibody therapy in PDAC. (PMID:41935073)
  • Anti-PD-1-based strategies can promote CD8+ T-cell responses, including synergy with fpPRPS and enhanced checkpoint immunotherapy in preclinical models. (PMID:41998161, PMID:41975460)
  • Ipilimumab was reported to enable robust activation of primed CD8+ T cells, supporting their role in checkpoint-responsive immunity. (PMID:41989053)
  • CD8+ T-cell responses were enriched in BANF1-high tumors by CIBERSORT analysis, suggesting an association with tumor immune landscape features. (PMID:42000935)

Tumor immune suppression and dysfunction

  • In KRAS-mutated biliary tract cancer, CD8+ T-cell infiltration and interactions with antigen-presenting cells were reduced, indicating impaired antitumor immunity. (PMID:41186264)
  • Altered lipid metabolism in the tumor microenvironment was linked to dysfunctional antitumor CD8+ T cells. (PMID:41946907)
  • Glycocholic acid suppressed CD8+ T-cell-mediated immunity in a colorectal cancer model, and blocking this signaling potentiated immune checkpoint therapy. (PMID:41935049)
  • Fc-intact anti-PD-1 therapy caused selective depletion of PD-1+ virus-specific and tumor-specific CD8 T cells from the liver via FcγR III. (PMID:41950082)

Cell trafficking, expansion, and tissue-resident memory

  • Intestine-specific Ddr1 knockout increased CD8+ T-cell infiltration in mouse colorectal cancer models. (PMID:41962054)
  • Cryoablation expanded effector CD8+ T cells and was associated with immune stimulation in combination approaches. (PMID:41989053)
  • STING agonist delivery via engineered silicasomes expanded cytotoxic and memory T-cell populations, including CD8+ T cells. (PMID:41955504)
  • Peripheral vaccination generated brain-resident memory CD8+ T cells that durably protected mice against intracranial malignancy. (PMID:41983390)

Delivery, imaging, and combination therapy

  • CD8+ T cells were isolated, labeled with SPIO, and tracked by MRI in a preclinical ovarian cancer model, enabling noninvasive immune-cell imaging. (PMID:41957244)
  • Inhalable LNT-DOX formulation recruited cytotoxic T cells into the tumor microenvironment, supporting local chemoimmunotherapy. (PMID:41947504)
  • A “one-two punch” strategy to reverse immunosuppressive metabolism enhanced T-cell immunity and checkpoint immunotherapy, consistent with CD8+ T-cell activation. (PMID:41975460)
  • fpPRPS promoted CD8+ T-cell responses and was further enhanced by anti-PD-1 treatment in mice. (PMID:41998161)