CD8+ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity

Abstract

Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Cancer immunotherapy seeks to recruit an effective immune response to eliminate tumor cells. To date, cancer vaccines have shown only limited effectiveness because of our incomplete understanding of the necessary effector cells and mechanisms that yield efficient tumor clearance. CD8+ T cell cytotoxic activity has long been proposed as the primary effector function necessary for tumor regression. However, there is increasing evidence that indicates that components of the immune system other than CD8+ T cells play important roles in tumor eradication and control. The following review should provide an understanding of the mechanisms involved in an effective antitumor response to guide future therapeutic designs. The information provided suggests an alternate means of effective tumor clearance in malignant glioma to the canonical CD8+ cytotoxic T cell mechanism.

Expression of a novel CNPY2 isoform in colorectal cancer and its association with oncologic prognosis

“…Furthermore, Saposin B also facilitated antigen cross-presentation by disintegrating membranes of apoptotic vesicles in recipient dendritic cells (DCs), resulting in activated subsequent CD8+ T cell responses [ 21 ]. It was clear that both NKT and CD8+ T cells acted as a direct killer to eliminate tumor cells and impede tumor progression [ 22 , 23 ]. Therefore, patients with lower CNPY2 isoform2 expression might have weaker immunological responses to conquer tumor progression, which could translate into a poorer survival outcome.…”

Microenvironment-derived ADAM28 prevents cancer dissemination

“…Hence, the adaptive immune system provides an effective response against tumors, mainly mediated by CD8 + cytotoxic T lymphocytes (CTLs), which induce tumor cell death through perforin-Granzyme release or via Fas/FasL pathway [13]. CD4 + T cells also play critical roles in anti-tumor responses as they indirectly stimulate CD8 + T cells by secreting pro-inflammatory cytokines that support CD8 + T cell activities [14]. In this context, infiltration of human lung tumors by CTLs has been significantly correlated with an improved outcome of NSCLC patients [15–21].…”

Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists

“…Indeed, it has already been shown that NKT and NK cells express NOD1, and their stimulation with NOD1 agonist induces a strong IFN-γ production and enhances their cytotoxic activity. [58][59][60] However, the stimulation of innate subsets was not efficient enough in this model, which requires a strong and specific antitumor immunity to generate a solid therapeutic effect.…”