Abstract:Although classical Hodgkin lymphoma (CHL) is typically curable, 15–25% of individuals eventually experience a relapse and pass away from their disease. In CHL, the cellular microenvironment is constituted by few percent of H/RS (Hodgkin/Reed–Sternberg) tumor cells surrounded from a heterogeneous infiltration of inflammatory cells. The interplay of H/RS cells with other immune cells in the microenvironment may provide novel strategies for targeted immunotherapies. In this paper we analyzed the microenvironment … Show more
“…Classical Hodgkin lymphoma (cHL) is characterized by a small percentage of malignant Hodgkin and Reed-Sternberg (HRS) cells that are of mature B-cell origin, embedded within a highly immunosuppressive, HRS-induced TME ( 143 ). Despite recent advances, patients with R/R cHL, especially those with prior exposure to CD30-ADC brentuximab vedotin and checkpoint inhibitors, still have a dismal prognosis.…”
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 in B-cell non-Hodgkin lymphoma (NHL) validates the utility of CAR-based therapy for lymphomatous malignancies. Despite the success, treatment failure due to CD19 antigen loss, mutation, or down-regulation remains the main obstacle to cure. On-target, off-tumor effect of CD19-CAR T leads to side effects such as prolonged B-cell aplasia, limiting the application of therapy in indolent diseases such as chronic lymphocytic leukemia (CLL). Alternative CAR targets and multi-specific CAR are potential solutions to improving cellular therapy outcomes in B-NHL. For Hodgkin lymphoma and T-cell lymphoma, several cell surface antigens have been studied as CAR targets, some of which already showed promising results in clinical trials. Some antigens are expressed by different lymphomas and could be used for designing tumor-agnostic CAR. Here, we reviewed the antigens that have been studied for novel CAR-based therapies, as well as CARs designed to target two or more antigens in the treatment of lymphoma.
“…Classical Hodgkin lymphoma (cHL) is characterized by a small percentage of malignant Hodgkin and Reed-Sternberg (HRS) cells that are of mature B-cell origin, embedded within a highly immunosuppressive, HRS-induced TME ( 143 ). Despite recent advances, patients with R/R cHL, especially those with prior exposure to CD30-ADC brentuximab vedotin and checkpoint inhibitors, still have a dismal prognosis.…”
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 in B-cell non-Hodgkin lymphoma (NHL) validates the utility of CAR-based therapy for lymphomatous malignancies. Despite the success, treatment failure due to CD19 antigen loss, mutation, or down-regulation remains the main obstacle to cure. On-target, off-tumor effect of CD19-CAR T leads to side effects such as prolonged B-cell aplasia, limiting the application of therapy in indolent diseases such as chronic lymphocytic leukemia (CLL). Alternative CAR targets and multi-specific CAR are potential solutions to improving cellular therapy outcomes in B-NHL. For Hodgkin lymphoma and T-cell lymphoma, several cell surface antigens have been studied as CAR targets, some of which already showed promising results in clinical trials. Some antigens are expressed by different lymphomas and could be used for designing tumor-agnostic CAR. Here, we reviewed the antigens that have been studied for novel CAR-based therapies, as well as CARs designed to target two or more antigens in the treatment of lymphoma.
“…Higher number of CD68 + TAMs and microvessels in the non-responder versus the responder groups [ 78 ]…”
Section: Personal Experience (Table
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confidence: 99%
“…4 D, E, F), suggesting that the immunological escape in refractory CHL patients involved a greater number of macrophages. Additionally, the findings suggested that microvascular density could be used to evaluate angiogenic activity and aggressiveness in NHL subtypes [ 78 ]. Fig.…”
A link exists between chronic inflammation and cancer and immune cells, angiogenesis, and tumor progression. In hematologic malignancies, tumor-associated macrophages (TAMs) are a significant part of the tumor microenvironment. Macrophages are classified into M1/classically activated and M2/alternatively activated. In tumors, TAMs are mainly constituted by M2 subtype, which promotes angiogenesis, lymphangiogenesis, repair, and remodeling, suppressing adaptive immunity, increasing tumor cell proliferation, drug resistance, histological malignancy, and poor clinical prognosis. The aim of our review article is to define the role of TAMs and their relationship with the angiogenesis in patients with lymphoma reporting both an analysis of main published data and those emerging from our studies. Finally, we have discussed the anti-angiogenic approach in the treatment of lymphomas.
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