Fig. 3
From: Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes
Modifying CD8+ T response in cancer. (A) Immune checkpoint blockade radically changes the CD8+ T landscape via mobilisation of the stem-like populations, which primarily occurs in the company of supportive cells in the TDLNs and microenvironmental niches. Cancer cell death as a result of amplified response fosters a self-amplifying cycle owing to tumour antigen release and subsequent increased uptake and priming by APCs. ICBs can simultaneously stimulate TRM, which contributes to increased tumour killing and long-lasting immunosurveillance that deters recurrence and metastasis. (B) In addition to the conventional steps implicated in adoptive cell therapies (lymphocyte procurement, isolation, activation and expansion, pre-infusion lymphodepletion and post-infusion IL-2 administration), there have been multiple strategies in the phases of ex vivo manipulation and in vivo augmentation (marked with plus signs) to maximise the utility of transferred cells. A deeper understanding of the transcriptional, epigenetic, and metabolic controls of CD8+ T phenotypes will shed light on novel ways to engineer cells for the desirable attributes.