Fundamentals of immunology for understanding immunotherapy for lymphoma

An effective antitumor immune response in patients with lymphoma would eradicate the malignant B cells and cure the patient of the disease. This, however, does not occur, and a suboptimal antitumor response results in persistence and subsequent progression of the patient’s disease. The goals of immunotherapy are therefore to restore an effective antitumor immune response by promoting immune recognition, optimizing immune activation, and supporting persistence of the immune response resulting in subsequent immunological memory. Multiple mechanisms, however, are present within the tumor microenvironment that account for an inadequate immune response. These include loss of major histocompatibility complex expression on tumor cells and subsequent inadequate antigen presentation, increased expression of immunosuppressive ligands on malignant cells, populations of immune cells with suppressive function present in the tumor, and cytokines secreted by the malignant cell or other cells in the microenvironment that promote immune exhaustion or suppress the immune response. Successful immunotherapeutic strategies are specifically addressing these issues by promoting antigen presentation, improving recognition of the malignant cell, directly activating T cells and natural killer cells, and blocking immune checkpoint signaling that would suppress the immune response. Many of these approaches have proven highly successful in patients with various subtypes of lymphoma and are now being incorporated into standard clinical practice.

Fundamentals of immunology for understanding immunotherapy for lymphoma

An effective antitumor immune response in patients with lymphoma would eradicate the malignant B cells and cure the patient of the disease. This, however, does not occur, and a suboptimal antitumor response results in persistence and subsequent progression of the patient’s disease. The goals of immunotherapy are therefore to restore an effective antitumor immune response by promoting immune recognition, optimizing immune activation, and supporting persistence of the immune response resulting in subsequent immunological memory. Multiple mechanisms, however, are present within the tumor microenvironment that account for an inadequate immune response. These include loss of major histocompatibility complex expression on tumor cells and subsequent inadequate antigen presentation, increased expression of immunosuppressive ligands on malignant cells, populations of immune cells with suppressive function present in the tumor, and cytokines secreted by the malignant cell or other cells in the microenvironment that promote immune exhaustion or suppress the immune response. Successful immunotherapeutic strategies are specifically addressing these issues by promoting antigen presentation, improving recognition of the malignant cell, directly activating T cells and natural killer cells, and blocking immune checkpoint signaling that would suppress the immune response. Many of these approaches have proven highly successful in patients with various subtypes of lymphoma and are now being incorporated into standard clinical practice.

Tumor Immunology

The immune system has effectively evolved to protect the host against foreign invaders, including bacterial, viral, and parasitic infiltrates. Less clear has been the interaction and the protective effects the immune system mounts against its own infiltrates: cancer cells. Here we consider the dynamic interactions between cancer and the associated host immune response by highlighting the key players involved in engaging an effective antitumor immune response and the mechanisms responsible for enabling the evolution of cancer cells to escape immunosurveillance. By developing an appreciation for the dual function of the immune system in the setting of cancer biology, we also consider the clever strategies that have been employed to uncover tumor targets, including tumor-associated antigens and the mechanisms for enhancing or reengaging the immune system to mount an effective antitumor immune response. Finally, we incorporate these key findings into the context of immunotherapy, a rapidly evolving field aimed at combating tumor escape by enabling the host immune system to regain its tumor-eradicating functions. This review contains 5 figures, 9 tables and 60 references Key words: adoptive T cell therapy, checkpoint inhibitors, cytokine therapy, immunotherapy, neutralizing antibodies, tumor immunity, tumor microenvironment, vaccines

Tumor Immunology

The immune system has effectively evolved to protect the host against foreign invaders, including bacterial, viral, and parasitic infiltrates. Less clear has been the interaction and the protective effects the immune system mounts against its own infiltrates: cancer cells. Here we consider the dynamic interactions between cancer and the associated host immune response by highlighting the key players involved in engaging an effective antitumor immune response and the mechanisms responsible for enabling the evolution of cancer cells to escape immunosurveillance. By developing an appreciation for the dual function of the immune system in the setting of cancer biology, we also consider the clever strategies that have been employed to uncover tumor targets, including tumor-associated antigens and the mechanisms for enhancing or reengaging the immune system to mount an effective antitumor immune response. Finally, we incorporate these key findings into the context of immunotherapy, a rapidly evolving field aimed at combating tumor escape by enabling the host immune system to regain its tumor-eradicating functions. This review contains 5 figures, 9 tables and 60 references Key words: adoptive T cell therapy, checkpoint inhibitors, cytokine therapy, immunotherapy, neutralizing antibodies, tumor immunity, tumor microenvironment, vaccines