CD4+ T cell help in cancer immunology and immunotherapy

Abstract

Cancer immunotherapy aims to promote the activity of cytotoxic T lymphocytes (CTLs) within a tumour, assist the priming of tumour-specific CTLs in lymphoid organs and establish efficient and durable antitumour immunity. During priming, help signals are relayed from CD4 T cells to CD8 T cells by specific dendritic cells to optimize the magnitude and quality of the CTL response. In this Review, we highlight the cellular dynamics and membrane receptors that mediate CD4 T cell help and the molecular mechanisms of the enhanced antitumour activity of CTLs. We outline how deficient CD4 T cell help reduces the response of CTLs and how maximizing CD4 T cell help can improve outcomes in cancer immunotherapy strategies.

CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review

“…CD70 can be induced in the DCs for pursuing such a purpose (Bullock & Yagita, ). The receptor for CD70 is CD27 expressed in CTLs that mediates the first step of CTL priming (Borst et al, ). Other key functions for DCs in influencing CTL priming has been previously discussed in the related section.…”

IFN-Stimulated Gene 15 Is an Alarmin that Boosts the CTL Response via an Innate, NK Cell–Dependent Route

“…Then, cell samples were centrifuged for 5 min at 400 3 g and resuspended in FACS buffer (PBS with 2% FCS; Antibody Production Services). Surface staining with relevant mAbs and allophycocyanin-H-2D b /E7 [49][50][51][52][53][54][55][56][57] tetramers was performed for 30 min on ice. Intracellular staining was performed after cell fixation and permeabilization using Foxp3 Transcription Factor Staining Buffer Set (eBioscience).…”

“…Fluorochrome-labeled mAbs employed were as follows: anti-CD8a-V500 . To detect cytokine production by E7 49-57 -specific CD8 + T cells in dLN and spleen, cells were incubated for 16 h with 1 mg/ml E7 [49][50][51][52][53][54][55][56][57] or no peptide (negative control) in the presence of GolgiPlug (BD Biosciences) in IMDM supplemented with 8% FCS. Flow cytometry was performed using LSRFortessa (BD Biosciences), and data were analyzed with FlowJo software (Tree Star).…”

“…To examine CD8 + T cell activation, we used a DNA vaccine-encoding HPV-16 E7 protein in a shuffled configuration (E7SH) (37,38). This protein contains an immunodominant epitope, E7 [49][50][51][52][53][54][55][56][57] , that is presented by H-2D b (Fig. 2B).…”

Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8+ T cells

“…Upon activation,effector CTLs infiltrate the core or invasive site of the tumour to produce efficient and durable anti‐tumour immune effects . CD4 + T helper cells play an essential role in CD8 + cytotoxic T lymphocytes mediated immune response, promoting both effector functions and the priming of CTLs . The activation of T cells requires a dual signal system.…”