Abstract INTRODUCTION Immunity in cancer patients is modified both by the cancer itself and by oncospecific treatments. Whether a patient’s adaptive immunity is impaired depends on their levels of naive lymphocytes and other cell populations. During the COVID-19 pandemic, cancer patients are at greater risk of progressing to severe forms of the disease and have higher mortality rates than individuals without cancer, particularly while they are receiving cancer-specific therapies. An individual’s protection against infection, their response to vaccines, and even the tests that determine the humoral immune response to SARS-CoV-2, depend on lymphocyte populations, meriting their study. OBJECTIVE Estimate blood concentrations of lymphocytes involved in the immune response to new pathogens in cancer patients. METHODS We carried out an analytical study of 218 cancer patients; 124 women and 94 men, 26–93 years of age, who were treated at the National Oncology and Radiobiology Institute in Havana, Cuba, March–June, 2020. Patients were divided into five groups: (1) those with controlled disease who were not undergoing cancer-specific treatment; (2) those undergoing debulking surgery; (3) patients undergoing chemotherapy; (4) patients undergoing radiation therapy and (5) patients currently battling infection. We evaluated the following peripheral blood lymphocyte subsets via flow cytometry: B lymphocytes (total, naive, transitional, memory, plasmablasts and plasma cells); T lymphocytes (total, helper, cytotoxic and their respective naive, activated, central memory and effector memory subsets); and total, secretory and cytotoxic natural killer cells and T natural killer cells. We also estimated neutrophil/lymphocyte ratios. Lymphocyte concentrations were associated with controlled disease and standard cancer therapy. For variables that did not fall within a normal distribution, ranges were set by medians and 2.5–97.5 percentiles. The two-tailed Mann–Whitney U test was used to measure the effect of sex and to compare lymphocyte populations. We calculated odds ratios to estimate lymphopenia risk. RESULTS All cancer patients had lower values of naive helper and cytotoxic T lymphocyte populations, naive B lymphocytes, and natural killer cells than normal reference medians. Naive helper T cells were the most affected subpopulation. Memory B cells, plasmablasts, plasma cells, activated T helper cells, and cytotoxic central memory T cells were increased. Patients undergoing treatment had lower levels of naive lymphocytes than untreated patients, particularly during radiation therapy. The risk of B lymphopenia was higher in patients in treatment. The odds ratio for B lymphopenia was 8.0 in patients who underwent surgery, 12.9 in those undergoing chemotherapy, and 13.9 in patients in radiotherapy. CONCLUSIONS Cancer and conventional cancer therapies significantly affect peripheral blood B lymphocyte levels, particularly transitional T helper lymphocytes, reducing the immune system’s ability to trigger primary immune responses against new antigens.
As part of the stage I clinical trial with the murine monoclonal antibody IOR-T1 at repeated doses (200-800 mg) in patients carriers of cutaneous T-cell lymphoma, the pharmacokinetics and the response against the mouse protein (HAMA) were studied in the 10 patients under treatment. It was observed a great individual variation in the maximum concentration in serum, which was estimated at 2 hours. The mean life time of the monoclonal antibody was between 13.93 and 19.6 hours. Most of the patients developed antibodies against the monoclonal antibody IOR-T1. The presence of this second antibody did not alter signficantly the pharmacokinetics of the administered monoclonal antibody.
Como parte del ensayo clínico fase I con el anticuerpo monoclonal murino IOR-T1 (AcM IOR-T1) con dosis repetidas (200-800 mg) en pacientes que padecían llinfoma T cutáneo, se estudió la farmacocinética y la respuesta contra la proteína del ratón (HAMA) en los 10 pacientes tratados. Se observó una gran variación individual en la concentración máxima en suero estimada a las 2 h. El tiempo de vida media del AcM fue entre 13,93 y 19,6 h. La mayoría de los pacientes desarrolló anticuerpos contra el AcM IOR-T1. La presencia de este segundo anticuerpo no alteró significativamente la farmacocinética del AcM administrado.
The cutaneous lymphomas are useful models for studying the etiopathogenic mechanisms of the lymphoproliferative diseases, since the samples of tissue are obtained through non invasive methods for the diagnosis and follow-up. Although the cutaneous T-cell lymphomas are developed from the T lymphocytes existing in the skin, other cells and diverse factors associated with the lymphoid tissues take part in the lymphomagenesis. The appearance of these lymphomas in the skin does not exclude the presence of malignant cells in the circulation and their development in other organs. Nowadays, the possibility of detecting the injuries in early stages and the accuracy of alterations in the T-cell receptor allows to extend the study of this disease.
Los linfomas cutáneos resultan modelos útiles para el estudio de los mecanismos patogénicos de las enfermedades linfoproliferativas dado que para el diagnóstico y el seguimiento, las muestras de tejido se obtienen a través de métodos no invasivos. Aunque los linfomas T cutáneos se desarrollan a partir de los linfocitos T residentes en la piel, otras células y diversos factores asociados al tejido linfoide participan en la linfomagénesis. La aparición de estos linfomas en la piel no excluye la presencia de células malignas en la circulación y su desarrollo en otros órganos. Actualmente, la posibilidad de detectar las lesiones en estadios tempranos y la precisión de alteraciones en el receptor de células T permite ampliar el estudio de esta enfermedad.
The capacity of the soluble mediators released during the activation of T lymphocytes to potentiate the response of natural cytotoxicity was studied in a group of 12 patients with breast cancer (5, stage IIa; 2, stage IIb; 2, stage III; and 3, stage IV) This activation was performed with IORT3, IORT1, anti-CD3 and anti-CD6 monoclonal antibodies, respectively. As a result, it was observed a reduction of the cytotoxic activity of peripheral mononuclear cells induced by the mediators released during CD3/CD6 activation mainly among patients in the most advanced stages (III and IV), which differs completely from what was analyzed in sound controls and in most of the stage II patients.
Se estudió en un grupo de 12 pacientes con cáncer de mama (5 pacientes de estadio IIa, 2 de estadio IIb, 2 de estadio III y 3 de estadio IV) la capacidad de los mediadores solubles liberados durante la activación de linfocitos T para potenciar la respuesta de citotoxicidad natural. Dicha activación se realizó con los anticuerpos monoclonales (AcMs) IORT3 e IORTL, anti-CD3 y anti-CD6 respectivamente. Como resultado se observó una disminución de la actividad citotóxica de células mononucleares periféricas inducida por los mediadores liberados durante la activación CD3/CD6 en las pacientes principalmente en los estadios más avanzados (III y IV), lo que difiere totalmente de lo analizado en controles sanos y en la mayoría de las pacientes en estadio II.