RESUMO
Evading immune eradication is a prerequisite for neoplastic progression and one of the hallmarks of cancer. Here, we review the different immune escape strategies of lymphoma and classify them into two main mechanisms. First, lymphoma cells may "hide" to become invisible to the immune system. This can be achieved by losing or downregulating MHC and/or molecules involved in antigen presentation (including antigen processing machinery and adhesion molecules), thereby preventing their recognition by the immune system. Second, lymphoma cells may "defend" themselves to become resistant to immune eradication. This can be achieved in several ways: by becoming resistant to apoptosis, by expressing inhibitory ligands that deactivate immune cells and/or by inducing an immunosuppressive (humoral and cellular) microenvironment. These immune escape mechanisms may have therapeutic implications. Their identification may be used to guide "personalized immunotherapy" for lymphoma.
Assuntos
Evasão da Resposta Imune , Imunoterapia/métodos , Linfoma/imunologia , Apresentação de Antígeno , Apoptose , Humanos , Linfoma/terapia , Microambiente Tumoral/imunologiaRESUMO
Ibrutinib, a first-class Bruton tyrosine kinase inhibitor, is known to be associated with adverse bleeding events and has been recently approved for the treatment of relapse Waldenström macroglobulinemia (WM). Here, we report the exhaustive clinical and biological follow-up of 2 patients treated by ibrutinib alone in the context of relapsed WM with an acquired von Willebrand syndrome (AVWS) complication. In two cases, ibrutinib has been shown to be quickly efficient and safe for treating both AVWS and its underlying condition the WM, without bleeding complications. Interestingly, ibrutinib treatment brings a rapid and extended over time normalization of von Willebrand factor clearance. These observations show that ibrutinib is a valuable therapeutic option in relapsed WM patients associated with AVWS and highlighting the need for further cohort studies with long-term follow-up of patients to confirm the efficacy and safety of a treatment by ibrutinib for WM patients with AVWS complication.
Assuntos
Macroglobulinemia de Waldenstrom , Doenças de von Willebrand , Humanos , Recidiva Local de Neoplasia , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológico , Doenças de von Willebrand/etiologia , Piperidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológicoRESUMO
CASE PRESENTATION: An 80-year-old-woman was referred for evaluation of chest pain that appeared after providing care at home for her sick husband, which included helping him to get up and move about. The pain was initially triggered by lifting heavy objects but then became constant, without exacerbating or relieving factors. The pain was located in the left hemithorax and was not associated with shortness of breath or cough. Because the patient did not feel any better after a month, her general practitioner ordered a radiograph, which revealed a suspicious pulmonary nodule in the left upper lobe. She was a lifelong nonsmoker and denied any drug abuse. She had not been professionally exposed to lung carcinogens. She had a medical history of type 2 diabetes, ischemic cardiomyopathy, and renal artery stenosis. Her father died of lung cancer. She resided in Lille, France, and did not report any recent travel.
Assuntos
Histiocitose/patologia , Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Idoso de 80 Anos ou mais , Dor no Peito , Feminino , Histiocitose/complicações , Histiocitose/diagnóstico , Humanos , Cadeias kappa de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/imunologia , Corpos de Inclusão/imunologia , Corpos de Inclusão/ultraestrutura , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/cirurgia , Lisossomos/ultraestrutura , Microscopia Eletrônica , Tomografia por Emissão de Pósitrons , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
Downregulation/loss of the antigen presentation is a major immune escape mechanism in cancer. It allows tumour cells to become 'invisible' and avoid immune attack by antitumour T cells. In tumour harbouring properties of professional antigen presenting cells (i.e. tumour B cells in lymphoma), downregulation/loss of the antigen presentation may also prevent direct priming of naïve T cells by tumour cells. Here, we review treatments that may induce/restore antigen presentation by the tumour cells. These treatments may increase the generation of antitumour T cells and/or their capacity to recognise and eliminate tumour cells. By forcing tumour cells to present their antigens, these treatments may sensitise patients to T cell-based immunotherapies, including checkpoint inhibitors.