Immune profiling is important for understanding cancers
The adaptive immune system plays a vital role in cancer biology. Several areas of profiling the immune repertoire have demonstrated value in oncology research, including T- and B-cell clonalities, MRD determination, tumor infiltrating lymphocyte quantification, and somatic hypermutation analysis.
Unique T and B-cell receptors (TCRs and BCRs) are generated via the process of V(D)J somatic recombination to create a diverse array of sequences in B and T cells (Figure 1). Interrogating BCRs and TCRs via NGS provides insights into potentially malignant clones. While TCRs are comprised of alpha, beta, gamma, and delta chains, B-cell receptors are comprised of heavy and light chains (Figure 1). These unique genomic sequences are fingerprints of T or B-cell clonotypes and can be used to track MRD in lymphoid malignancy research.
Tumor infiltrating lymphocytes (TILs) are an important biomarker in several solid tumors, including lung, breast, colon, melanoma, sarcoma, and gliomas. Their presence and quantification can be helpful to understand tumor behavior. For example, the quantification of TILs in breast cancer has led to the definition of lymphocyte-predominant breast cancer (50-60% TILs), which is associated with tumor senescence .
Somatic hypermutation analysis has been a valuable biomarker in B-cell lymphoma. Immunoglobulin heavy chain (IGH) gene rearrangements acquire somatic hypermutations upon exposure to an antigen, which is a normal development in B-cells. Researchers have found that the somatic hypermutation status of a malignant B-cell clone is a useful biomarker to stratify disease states in chronic lymphocytic leukemia (CLL). It has been demonstrated that CLL populations with high somatic hypermutation (often referred to as “mutated”) have less aggressive behavior , while more aggressive disease is associated with B-cell tumors without somatic hypermutation. BCR constant region class switching is an additional area of oncology research.