Med Clin (Barc). 2020;154(12):493–495 www.elsevier.es/medicinaclinica Editorial article Clinical surveillance in immunotherapy-treated patient  Vigilancia clínica de los pacientes que reciben inmunoterapia Javier Molina-Cerrillo * , Teresa Alonso-Gordoa Servicio de Oncología Médica, Hospital Universitario Ramón y Cajal, Madrid, Spain Immunotherapy has become a promising cancer strategy in recent years with positive results in phase III studies in a growing number of tumour types, from lung or kidney cancer to some types of haematological malignancies. The objective of this editorial is to provide information on how these new drugs work to establish the appropriate clinical follow-up throughout use. All this, will allow to identify in an early way the possible adverse events derived and the correct management of the same. 1–4 We now know that the immune system plays a key role not only in the control of bacterial, viral or parasitic infectious diseases, but behaves as a leading player in the progression and control of tumour disease. Furthermore, we know that its role is important in all phases of the disease, both in its initial part and in the more advanced stages. The immune system is capable of recognizing tumour cells in their development and prevents their prolifera- tion and survival. Unfortunately, this mechanism does not always work perfectly, due to failure in antigen presentation or due to the development of tumour immune escape mechanisms. These mech- anisms allow neoplastic cells to escape the control of the immune system and, therefore, to proliferate and develop. Lymphocyte activation is an extremely complex process that requires perfect orchestration of the immune system. Thus, for acti- vation of the CD8+ T-cell, the end effector of cytotoxic activity, a number of mechanisms are required. First, the presentation of the antigen by the antigen-presenting cell to the T-cell receptor. This lymphocyte synapse is necessary, but not sufficient for final lymphocyte activation. Co-stimulation is required between CD28 T cell and B7/B7.1 of the antigen-presenting cell. 5 At this time, the cytotoxic T-cell is activated and can exert its function, recogniz- ing the antigen against which it has been activated and, therefore, acting accordingly against its environment. But the immune sys- tem has generated mechanisms to modulate the effector response of cytotoxic T-cells to prevent their over-activation with possible deleterious autoimmune effects. In this sense, the CD8+ T-cell itself, when activated, begins to express inhibitory proteins such as CTLA- 4 on its surface. The latter’s mission is to compete with CD28 in its union with B7 in order to inactivate the T-cell, thus modulat- ing its cytotoxic activity and therefore acting as a self-regulator  Please cite this article as: Molina-Cerrillo J, Alonso-Gordoa T. Vigilancia clínica de los pacientes que reciben inmunoterapia. Med Clin (Barc). 2020;154:493–495. * Corresponding author. E-mail address: javier.molinace@gmail.com (J. Molina-Cerrillo). for the immune system’s cytotoxic capacity. 6 That is why the first immunotherapy drug of the modern era was developed to block CTLA-4 by preventing its competition with B7, thus making it dif- ficult to inactivate the cytotoxic T-cell. This drug is ipilimumab, which initially demonstrated efficacy in melanoma and later in other solid tumors. 1 Subsequently, other control points that regulate the activa- tion/inactivation of said CD8+ T-cells have been identified. Among them, PD-1 inhibitors stand out, followed by PD-L1. As with CTLA- 4, the activated T-cell mainly co-expresses PD-1 on its surface. Its PD-L1 ligand is expressed mainly in cells of the immune system but also in tumour cells. The binding of PD-1 and PD-L1 triggers an inhibitory response in the lymphocyte, leading to its inactivation. This expression mechanism in PD-L1 by the tumour is the result of a masking strategy and therefore of tumour escape from immune response and control. 7 These drugs against PD-1 (nivolumab or pembrolizumab) and PD-L1 (durvalumab, atezolizumab, avelumab, among others) have shown even greater efficacy than CTLA-4 inhibitors with a more manageable toxicity profile. Currently, the combination of both mechanisms of action against PD-1 and CTLA-4 has already shown greater efficacy than standard treatments for various metastatic tumours, among which melanoma and kidney cancer stand out. 8,9 Pharmacological intervention on the immune system is not something new in oncology. Several decades ago, for example, interleukin 2 was used as an immune system activator with pub- lished cases of complete responses in patients with advanced kidney cancer. Other interleukins have also been used with inter- feron in melanoma. Both strategies have fallen into disuse today for 2 main reasons. On the one hand, their toxicity profile, diffi- cult to manage for proven results. On the other hand, the arrival of tyrosine kinase inhibitors and later the new immunotherapy drugs, more effective and with a better tolerance profile. Currently, CTLA-4 inhibitors and drugs against the PD-1/PD-L1 axis have been approved for use in our country. But the devel- opment of immunotherapy, far from being stagnant, continues today. We know that there are more control points in the acti- vation or deactivation of the cytotoxic lymphocyte, which is why drugs are being developed to maintain lymphocyte activation by acting against proteins such as LAG-3, TIM-3 or even OX-40, among others. 10 Therefore, with immunotherapy we have been able to reverse this ability to generate immune tolerance in lymphocytes by the 2387-0206/© 2020 Elsevier Espa ˜ na, S.L.U. All rights reserved.