What role does immune profiling play in non-Hodgkin’s lymphoma precision care?

Immune profiling plays a crucial and transformative role in the precision care of non-Hodgkin’s lymphoma (NHL) by providing detailed insights into the tumor’s immune environment, guiding personalized treatment strategies, and improving patient outcomes. At its core, immune profiling involves analyzing the types, states, and functions of immune cells and molecules within the tumor and the patient’s body, which helps clinicians understand how the immune system interacts with lymphoma cells and how these interactions influence disease progression and response to therapy.

Non-Hodgkin’s lymphoma is a diverse group of blood cancers originating mainly from B cells, which express specific surface markers such as CD19, CD20, and CD45. These markers have been targets for therapies like monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies. Immune profiling allows for the precise identification of these markers and the immune cells involved, enabling tailored treatments that specifically target the lymphoma cells while sparing healthy tissue.

One of the key contributions of immune profiling in NHL is its ability to characterize immune cell subsets within the tumor microenvironment. This includes cytotoxic CD8+ T cells, which can kill cancer cells, regulatory T cells that may suppress immune responses, and tumor-associated macrophages that can either support or inhibit tumor growth. By understanding the balance and functional states of these cells, clinicians can predict how the tumor might evade immune attack or respond to immunotherapies. For example, a high presence of exhausted T cells or immunosuppressive macrophages might indicate a tumor that is resistant to certain treatments, prompting the use of alternative or combination therapies.

Immune profiling also assesses the expression of immune checkpoint molecules such as PD-L1 on tumor cells or immune cells. PD-L1 expression is a critical biomarker because it can suppress T-cell activity and allow the tumor to escape immune destruction. Therapies that block the PD-1/PD-L1 pathway have shown promise in restoring anti-tumor immunity. Monitoring PD-L1 levels through immune profiling helps determine which patients are likely to benefit from checkpoint inhibitors and tracks how well these therapies are working during treatment.

Beyond cell types and checkpoint molecules, immune profiling evaluates molecular changes such as cytokine levels and gene expression patterns related to immune function. Cytokines are signaling proteins that regulate immune responses, and their profiles can indicate whether the immune system is actively fighting the tumor or being suppressed. Gene expression analyses can reveal signatures associated with immune activation or resistance, providing early indicators of treatment response or failure. This molecular information complements clinical data and imaging, offering a more comprehensive picture of the disease.

In recent years, immune profiling has been integrated with advanced technologies like next-generation sequencing, flow cytometry, and multiplex immunohistochemistry, enabling highly detailed and dynamic assessments. For instance, longitudinal immune profiling—repeated assessments over time—can track how the immune landscape changes with treatment, helping to adjust therapies in real time. This approach is particularly valuable in managing relapsed or refractory NHL, where the disease evolves and may develop resistance to initial treatments.

One of the most exciting applications of immune profiling in NHL precision care is in the context of CAR T-cell therapy. CAR T-cell therapy involves engineering a patient’s own T cells to target specific lymphoma antigens such as CD19 or CD20. Immune profiling before and after CAR T-cell infusion can identify which patients are likely to respond, monitor the expansion and activity of CAR T cells, and detect early signs of immune-related side effects like cytokine release syndrome. For example, imaging studies using immune-related tracers can visualize activated immune cells in the tumor microenvironment, providing a non-invasive way to assess treatment efficacy.

Furthermore, immune profiling supports the development of novel therapeutic strategies such as dual-target CAR T cells that simultaneously recognize multiple lymphoma antigens, improving the chances of complete remission. It also aids in optimizing combination therapies that include radioimmunotherapy, checkpoint inhibitors, and ste