![]() This phenomenon has been reviewed extensively elsewhere 8, 9, 10. This disruption manifests most prominently in an expansion of immature neutrophils and monocytes in the periphery of tumour-burdened hosts, which then also traffic to the TME and contribute to local immunosuppression. Many human cancers and mouse models of cancer drive extensive disruption of haematopoiesis. ![]() Finally, we address the utility of peripheral immune biomarkers in aiding the diagnosis and prognosis of cancer and response to therapy. We also examine the critical contribution of peripheral immune cells to driving and sustaining efficacious immunotherapy responses and the capacity of the tumour-burdened immune system to orchestrate a new immune response. We outline the extensive reorganization of peripheral immune cells that coincides with malignant tumour outgrowth as well as the systemic immunological consequences of conventional therapies (surgery, chemotherapy, radiation). Here, we review recent advances that set the stage for a new holistic vantage point of tumour immunology to map and therapeutically harness the entirety of an immune response to cancer. Recent clinical and preclinical studies are beginning to unravel the range of systemic immune perturbations that occur during tumour development as well as the crucial contribution of peripheral immune cells to an antitumour immune response. Therefore, a thorough understanding of immune responses to cancer must encompass all immune cell lineages across the peripheral immune system in addition to within the TME. Furthermore, virtually every subset of immune cell has been implicated in cancer biology 6, 7. The localized antitumour immune response cannot exist without continuous communication with the periphery. For example, many myeloid cells are frequently replenished from haematopoietic precursors in the bone marrow 4, and critical T cell priming events typically occur in lymphoid tissues 5. The tumour immunology field has focused heavily on local immune responses in the tumour microenvironment (TME), yet immunity is coordinated across tissues. Further progress towards more broadly effective immunotherapeutic strategies requires a deeper understanding of the immunological relationships between tumours and their hosts across the body. To date, most immunotherapies have largely been used in patients with advanced cancers, and therefore the response rate in less advanced disease remains to be fully determined. Despite these successes, immunotherapy remains ineffective for most patients with cancer 2, 3. ![]() Moreover, infusion of expanded autologous tumour-specific T cells or chimeric antigen receptor T cells has proven effective in patients with leukaemia. Modulation of the existing patient immune system through immune checkpoint inhibitors (ICIs) such as anti-CTLA4, anti-PD1 and anti-PDL1 has led to durable remissions across a wide variety of different tumour types. Over the last decade, targeting the immune system with immunotherapy has revolutionized cancer therapy. Whether this inflammation initiates tumorigenesis or supports tumour growth is context dependent, but ultimately the global immune landscape beyond the tumour becomes significantly altered during tumour progression. Cancer is a systemic disease, and prolonged inflammation is a hallmark of cancer 1. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |