Mechanisms of Immune Escape in B-cell Lymphoma

Abstract

The immune system plays a major role in defending the body from infections and eliminating abnormal or malignant cells. However, in specific malignancies like B-cell lymphomas, this surveillance mechanism is frequently undermined. A major approach facilitating cancer immune evasion is the manipulation of immunological checkpoints regulatory pathways that restrict immune activation and maintain self-tolerance. Cancer cells exploit these checkpoints to inhibit immune recognition and clearance. A comprehensive understanding of these pathways is crucial for the advancement of next-generation targeted immunotherapies.

This research project explored two key immunoregulatory molecules: LILRB1 (Leukocyte Immunoglobulin-like Receptor B1) and TNIP1 (TNFAIP3-interacting protein 1). LILRB1 is an inhibitory receptor expressed on the surface of immune cells, including CD14⁺ monocytes and CD8⁺ cytotoxic T cells. Upon binding to ligands such as MHC-I or HLA-G, it transmits immunosuppressive signals that diminish activation through SHP phosphatase recruitment. TNIP1, a cytoplasmic molecule downstream of NF-κB, functions as a transcriptionally inducible suppressor that inhibits pro-inflammatory signaling by collaborating with A20 (Gasparini et al., 2014). Both molecules are increasingly acknowledged as factors in tumor-induced immune tolerance.

This study examined the alterations in TNIP1 expression in fresh peripheral blood samples from healthy donors following LILRB1 activation over a 48-hour period. Flow cytometry combined with quantitative analysis (Kaluza software) has been used to evaluate intracellular TNIP1 in both innate (monocytes) and adaptive (T cells) immune subsets. The findings revealed a time-dependent elevation in TNIP1 expression, particularly notable in CD14⁺ monocytes, suggesting a lineage-specific immunosuppressive mechanism triggered by LILRB1 interaction.

These findings offer new understanding of checkpoint-mediated immune evasion pathways relevant to B-cell lymphoma. They corroborate current data demonstrating that TNIP1 overexpression contributes to tumor-associated immunological dysfunction and propose that LILRB1–TNIP1 signaling offers a promising therapeutic target for intervention (Ramirez et al., 2012).