Cancer Immunotherapy: An increasing emphasis on CD4+ T cells and MHC Class II Neoantigens

It is widely recognised that CD8+ T cells play a crucial role in facilitating anti-tumour immunity by identifying tumour-associated antigens presented on major histocompatibility complex class I through their expressed T cell receptor. The majority of studies on cancer neoantigens have therefore concentrated on MHC class I restricted antigens that are recognised by CD8+ T cells. However, it is increasingly evident that CD8+ T cell binding neoantigens alone are insufficient to generate a potent anti-tumour response. A recent study conducted by Alspach et al. (1) demonstrated that the presence of CD4+ T cells, in addition to CD8+ T cells, is necessary for spontaneous and immunotherapy-induced anti-tumour responses (1).

Studies have shown that CD4+ T cells have an impact on fighting tumours through various mechanisms that depend on MHC class II neoantigens and the specific tumour environment. In certain cases, CD4+ T cells have been found to acquire cytotoxic activity in the presence of high levels of IL-2 or when IL-2 sequestering T Reg cells are absent (2). A recent investigation even reported that among supercentenarians, cytotoxic CD4+ T cells make up an average of 25% of T cells, suggesting their crucial role in protecting against infections and cancers, and potentially contributing to an extended disease-free life expectancy (3). As a result, there is currently a strong focus on understanding the complex interactions between cytotoxic and helper CD4+ lymphocytes with tumours and antigen-presenting cells, with particular interest in MHC class II-dependent immune activation mechanisms. MHC class II-restricted neoantigens now hold great potential as promising targets for cancer immunotherapies.

QuickSwitch™ Class II Tetramer Peptide Exchange and Quantitation Kit utilises a patented technique for exchanging up to ten peptides on an MHC Class II Tetramer. Reduce time and cost with this kit to create your own custom tetramers or to test which peptide sequence has the best peptide-MHC binding affinity. This kit can be used for screening multiple peptides or to create a small amount of your own custom Tetramer in-house. The resulting custom tetramers can be used for multiple applications including screening immunogenic peptides, neoantigen discovery, and many other assays downstream from in-silico selection.

REFERENCES:

1. Alspach, E. et al. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature 574: 696–701 (2019).
2. Śledzińska, A. et al. Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells. Immunity. 52(1):151-166 (2020).
3.  Hashimoto K. et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc Natl Acad Sci USA. 116(48):24242-24251 (2019).
4. Xiao, Jingyu, et al. “Engineering In Vitro Organ‐Structured Tumor Model for Evaluating Neoantigen‐Specific T Cell Responses in Hepatocellular Carcinoma.” Advanced Materials Interfaces (2023): 2300155.

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