CD4+ T Cells: Multitasking Cells in the Duty of Cancer Immunotherapy

Abstract

Cancer immunotherapy activates the immune system to specifically target malignant cells. Research has often focused on CD8+ cytotoxic T cells, as those have the capacity to eliminate tumor cells after specific recognition upon TCR-MHC class I interaction. However, CD4+ T cells have gained attention in the field, as they are not only essential to promote help to CD8+ T cells, but are also able to kill tumor cells directly (via MHC-class II dependent recognition) or indirectly (e.g., via the activation of other immune cells like macrophages). Therefore, immunotherapy approaches have shifted from only stimulating CD8+ T cells to targeting and assessing both, CD4+ and CD8+ T cell subsets. Here, we discuss the various subsets of CD4+ T cells, their plasticity and functionality, their relevance in the antitumor immune response in patients affected by cancer, and their ever-growing role in therapeutic approaches for human cancer.

Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis

“…As we all know, CD4 + T cells are important for the activation and expansion of CD8 + effectors, and also vital for the maintenance and generation of CD8 + T cell memory [ 8 ]. In the TME, they might also participate to amplify the CD8 + T cell response and have the ability to control tumor growth in different ways [ 8 ]. In our study, we found that CD4 + T cells were highly expressed in patient B but poorly expressed in patient C and patient D, implying that patient C and patient D had lower immunity.…”

“…[ 4 , 5 ]. Tumor cells and the components of TME, including CD8 + T cells [ 6 , 7 ], CD4 + T cells [ 8 , 9 ], NK cells [ 10 ], dendritic cells [ 11 , 12 ], B cells [ 13 , 14 ], macrophages [ 15 ], FOXP3 [ 16 ], and Collagen I [ 17 ] have close correlations to tumor treatment and prognosis. In past decades, due to the limitations of tools and clinical methodologies, it was difficult to analyze multiple components and assess tumor heterogeneity of the TME.…”

Regulation of T Cells in Cancer by Nitric Oxide

“…The expression of MHCII on the surface of APCs has a bound antigen peptide processed by the APC cells and the complex MHCII-bound peptide is recognized by the CD4 TCR that is specific for this complex. The interaction of the TCR and the MHCII complex results in the activation of the CD4 T cells along with co-stimulatory molecules on the APCs and the corresponding receptors on the CD4 T cells [10]. Naive T cells differentiate into one of several lineages of Th cells upon T cell receptor (TCR) activation, including Th1, Th2, Th9, and Th17 cells [9].…”

Irradiation Mediates IFNα and CXCL9 Expression in Non-Small Cell Lung Cancer to Stimulate CD8+ T Cells Activity and Migration toward Tumors

“…The literature has indicated that immunotherapy targeting PD-1 and CTLA-4 specifically increases CXCL9 and CXCL10 from tumor-associated macrophages in tumor tissues, whereas CXCL9 and CXCL10 are induced by IFNγ in the tumor microenvironment [27]. Therefore, another possibility for increasing CXCL9 in the nonCD8 + PBMCs was mediated by CD4 + T cells-secreted IFNγ since IFNγ is majorly secreted by CD4 + T cells, stimulated by antigen presenting cells [29].…”