Cancer Immunology

Cancer immunology, a field at the intersection of biology and immunology, investigates the immune system's involvement in cancer progression and development. Its primary focus is on cancer immunotherapy, leveraging immune responses for the treatment of cancer. Key aspects include cancer surveillance in animal models and the discovery of targets for immune recognition in human cancers.

Fig.1 Immune cell dynamics within the breast cancer tumor microenvironment.^{1, 5}

Tumor Antigen

Tumors can exhibit tumor antigens that elicit immune recognition and potentially trigger an immune reaction. These include:

• Tumor-specific antigens (TSAs): These antigens are exclusively found in tumor cells and can arise from oncoviral products (such as E6, E7, and EBNA-1) or aberrant products of mutated proto-oncogenes and oncogenes.
• Tumor-associated antigens (TAAs): Present in both healthy and tumor cells, TAAs encompass oncofetal antigens (such as AFP, CEA, and EGFR).

Fig.2 Sorts of tumor antigens.^{2, 5}

Applications of Cancer Immunology

Understanding the immune dynamics within the tumor microenvironment has highlighted immunotherapy as a potent clinical tool against various cancers. Strategies in cancer immunotherapy primarily involve blocking immune checkpoints, transferring engineered cells like T cells, natural killer cells, and macrophages, cytokine-based therapies, cancer vaccines, and oncolytic virus treatments. Additionally, therapies such as chimeric antigen receptor (CAR) T cell therapy demonstrate greater efficacy in hematologic malignancies like lymphoma, leukemia, and multiple myeloma compared to solid tumors.

Fig.3 Various cancer immunotherapy.^{3, 5}

Mechanisms of Tumor Immune Evasion

CD8⁺ cytotoxic T cells play a crucial role in anti-tumor immunity by recognizing antigens presented via MHC class I molecules. Upon binding, these cells initiate cytotoxic activities. Some cancer cells evade detection by reducing MHC class I expression through gene mutations or decreased sensitivity to IFN-γ, impacting antigen presentation. Additional evasion strategies include defects in antigen processing pathways like TAP or tapasin. Tumor cells also evade cytotoxic T cells by downregulating co-stimulatory molecules such as CD80 or CD86. Moreover, they express molecules like FasL and PD-L1 to induce T cell apoptosis or suppression. Resistance mechanisms involve inhibiting apoptotic pathways or upregulating antiapoptotic molecules like Bcl-2 and IAP.

Fig.4 Regulatory microenvironmental factors and antigen depletion drive tumor evasion.⁴