B&T Cell-Associated Lymphoma

Symptoms

Signs and symptoms of B&T cell lymphoma may include swollen lymph nodes in the neck, armpit, or groin; abdominal or chest pain, cough or difficulty in breathing, persistent fatigue, fever, night sweats, unexplained weight loss, etc.

Pathways

The occurrence and progression of lymphoma is multi-stage, along with multiple signaling pathways and cascade reactions involved. In B-cell lymphomas, dysregulated BCR signaling has been identified as a potent factor in lymphomagenesis and tumor survival. γ receptor-dependent cytokines and the JAK/STAT pathway play key roles in T cell immunity. Abnormal activation of this signaling pathway system is prevalent in T-cell lymphomas. Furthermore, many oncogenic events in lymphomas focus on the anti-apoptotic NF-κB pathway, together with further survival signals provided by the PI3K and JAK kinase pathways. Other molecular mechanisms involved in B&T-cell lymphomas include the TP53 pathway (involved in DNA repair mechanisms through negative regulation by CDKN2B/MDM2); B-cell lymphoma 2 (BCL-2) family regulates programmed cell death, and to help maintain tissue homeostasis; AKT and mTOR propagate PI3K activation signaling to downstream targets that mediate effects on cell cycle regulation; SYK activation can initiate signaling cascades, involved in NF-κB, PI3K, NF-AT, MAPK, and RAS signaling pathways leading to cell survival and proliferation, and other pathways.

Fig. 1 Signaling transduction pathways in lymphoma cells

Treatment

Chemotherapy, radiation therapy, bone marrow transplantation, targeted therapy, immunotherapy, and chimeric antigen receptor (CAR)-T cell therapy are common treatment strategies for B&T cell lymphoma.

• Examples of targeted therapy drugs:

1. Targeting lymphocyte antigen CD20: Rituximab, Ofatumumab and Obinutuzumab;
2. Target B cell receptor signaling pathways: Ibrutinib, Acalabrutinib, Copanlisib, Duvelisib and Idelalisib;
3. HDAC inhibitors: Belixostat, Vorinostat, Romidepsin;
4. Immune checkpoint inhibitors, such as PD-1 inhibitors (Nivolumab and Pembrolizumab), and PD-L1 inhibitors (Atezolizumab and Durvalumab), are the key targeted drug for the treatment of T cell lymphoma at present;

Fig. 2 PD-1 signaling

5. Bbrentuximab Vedotin (ADC), targeting CD30, for the treatment of CD30-positive relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and classic Hodgkin lymphoma (cHL).
6. Idelalisib, a PI3Kδ kinase inhibitor, induces apoptosis and inhibits the proliferation of malignant B cell lines/primary tumor cell lines. At the same time, it can also block a variety of signaling pathways and reduce the viability of tumor cells.

• Example of Chimeric Antigen Receptor Modified T Cell (CAR-T) Therapy:

Against CD19 antigens expressed on the surface of immature and mature B cells: Tisagenlecleucel and Axicabtagene clioleucel.