Immune impairment in patients with terminal cancers: influence of cancer treatments and cytomegalovirus infection

Abstract

Although immunodeficiency is usually considered a prerequisite of oncogenesis, a detailed immune pro- file in cancer has not yet been described. Without such profiling, it is not surprising that there is a vast discrepancy in the responses of cancer patients to immunotherapy. Our results show that the integrity of the immune system deteriorates with cancer progression by displaying a trend toward decreasing levels of functional T cells, including CD4, naïve, and central memory T cells, and an expansion of hyporesponsive populations such as CD28⁻ and CMV-specific T cells. One hundred and one patients constitute the study group for the observational study reported in this paper. Forty-eight patients with newly diagnosed stages III and IV and 53 patients with extensively treated stage IV disease. The costimulatory molecules CD27 and CD28 were downregulated in all patients. Among the proinflammatory cytokines (IL-6, TNF-α, IFN-γ), only IL-6 differed significantly among the groups, increasing as the cancer stage progressed. Plasma IL-7 did not diVer among the participants. The relative deficits of naïve T cells in cancer patients may be associated with the downregulation of IL-7Rα expression rather than changes in the circulating levels of IL-7. The downregulation of IL-7Rα expression was shown to be associated with increased levels of intracellular CMV. The present study suggests that the immune impairment in patients with cancer is associated with multiple factors, such as the stage of cancer, consequence of CMV infection and impact of treatment.

Cancer-Associated Immune Deficiency: A Form of Accelerated Immunosenescence?

“…Since CD4 T H cells play an important role in optimizing CD8 T cells activation, an adequate number of CD4 T H cells is therefore required to sustain the effector function against tumor cells by CD8 T cells. In normal adults, CD4 and CD8 T cells each constitute well over 20% of the total lymphocyte population, whereas the proportion of these cells in cancer patients is lower and appears to decline according to the cancer stage (Chen et al, 2010;Mozaffari et al, 2007). An inadequate amount of T cells indicates that cancer patients cannot generate a sufficient immune response, resulting in an increase in the frequency and severity of infectious diseases.…”

“…immunosurveillance evasion mechanism in which the immune system fails to eliminate tumors not because tumor antigens are absent, but rather that an inappropriate proportion of T lymphocytes with an "accelerated immunosenescence" status are present in cancer patients (Chen et al, 2010). Although cancer patients are often considered to have poor immunity, very few attempts have been made to examine the dysfunctional immune profile of these patients in detail.…”

Infecciones asociadas a la atención de salud en un Hospital de Oncología Brasileño: análisis de cinco años

“…Immunity deficit is characterized according to baseline pathology and age; dose and duration of immunosuppression therapy; epithelial integrity; humoral and cell immunological status; metabolic factors like bad nutrition; hyperglycemia and liver failure; abnormality of the mononuclear phagocyte system and presence of infections that modulate immunity, such as the Human Immunodeficiency Virus or cytomegalovirus (6,10) . Among the factors influencing infection development, the most common are: immunological status, age (newborns and elderly are more vulnerable), abuse of antibiotics, invasive procedures, immunosuppression and errors in infection control procedures (1,6,10) . During our study group's experience in practice and research at the Hospital Infection Control Service (SCIH) of a cancer hospital, it was verified that hospital infections in these patients present themselves differently.…”

Infecciones asociadas a la atención de salud en un Hospital de Oncología: el análisis de cinco años

“…Junto a esto, nuevos tratamientos amplían el grupo de pacientes con riesgo de infección y los tipos que pueden ser adquiridas (9) . El déficit inmune se caracteriza por la patología de base y edad; dosis y duración de la terapia inmunosupresora; integridad epitelial; status inmunológico humoral y celular; factores metabólicos como mala nutrición, hiperglicemia y disfunción hepática; anormalidad del sistema reticuloendotelial y presencia de infecciones que modulan la inmunidad, como el virus de la inmunodeficiencia humana o citomegalovirus (6,10) .…”

“…Sin embargo, tales avances permiten la aparición de eventos adversos e infecciosos por la agresión producida por la quimioterapia, radioterapia, inmunosupresores y reacciones de lo insertado en contra del paciente (6,10) .…”