RESUMEN
We investigated dynamic changes in T-lymphocyte subsets after hyperthermic intraperitoneal chemotherapy (HIPEC) or radiotherapy using flow cytometry. A total of 1423 lung cancer patients admitted to our hospital between October 2012 and July 2015 were enrolled, and age-matched healthy individuals served as controls. Peripheral blood mononuclear cells (PBMCs) were purified using standard Ficoll density gradient centrifugation, based on which CD3+, CD4+, and CD8+ T-cells were isolated. A surface marker was identified by flow cytometry. Immunohistochemical analysis determined the distribution of the cells in the tumor mass or adjacent tissues. A total of 957 patients (male: 555; female: 402; median age: 49.3 years) with lung cancer who had received only HIPEC or radiotherapy were enrolled. The patients were followed-up until death. No statistical difference was noticed between the patients who had received chemotherapy compared with the baseline levels. A remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy (78.71 ± 9.36 vs 68.15 ± 9.65, P < 0.05). The level of CD8+ in the patients who had received chemotherapy or radiotherapy was remarkably elevated in the post-treatment period (P < 0.05). The CD3+ and CD8+ T-cells were mainly expressed in the cytoplasm rather than in the adjacent tissues. The expression of CD3+ and CD4+ was correlated to tumor infiltration and metastasis. Remarkable elevation was noticed in the CD3+ T-cells in the patients three months after radiotherapy. The expression of CD3+ and CD4+ was negatively correlated to tumor infiltration and metastasis in non-small-cell lung cancer patients.
Asunto(s)
Leucocitos Mononucleares/inmunología , Neoplasias Pulmonares/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Femenino , Citometría de Flujo , Humanos , Hipertermia Inducida , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/efectos de la radiación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de la radiación , Linfocitos T/efectos de los fármacos , Linfocitos T/patología , Linfocitos T/efectos de la radiaciónRESUMEN
Ultraviolet (UV) radiation (UVR) produces deleterious effects that may finally lead to carcinogenesis. These adverse effects include tissue inflammation, free radical formation with consequent oxidation of proteins and lipids, DNA damage, and immune function suppression. The aim of this study was to evaluate the effects of UVR at the local and systemic levels following acute (4 consecutive days with 0.5 minimal erythema dose [MED]) or chronic (20 consecutive days with 0.25 MED) exposure. Locally, histological alterations and epidermal T-cell populations were studied. Systemically, inguinal lymph-node and spleen T cells were analyzed with respect to proliferative response and cytokine production against a nonspecific mitogen. Lymph-node T-cell populations were also characterized. Our results indicated that while both acute and chronic UVR produced epidermal hyperplasia and a decrease in epidermal T-cell density, acute UVR increased T-cell proliferative response, while chronic UVR produced the opposite effect, shifting the cytokine production toward a Th2/Treg profile. Therefore, even though acute irradiation produced a direct effect on skin, it did not correlate with a marked modification of overall T-cell response, which is in contrast to marked effects in chronically irradiated animals. These findings may contribute to understanding the clinical relevance of occupational UVR exposure, typically related to outdoor activities, which is associated with nonmelanoma skin carcinogenesis.
Asunto(s)
Piel/efectos de la radiación , Linfocitos T/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Citocinas/biosíntesis , Relación Dosis-Respuesta en la Radiación , Femenino , Citometría de Flujo , Ganglios Linfáticos/citología , Ganglios Linfáticos/efectos de la radiación , Activación de Linfocitos/efectos de la radiación , Ratones , Ratones Pelados , Piel/citología , Piel/inmunología , Bazo/citología , Bazo/efectos de la radiación , Subgrupos de Linfocitos T/fisiología , Subgrupos de Linfocitos T/efectos de la radiación , Linfocitos T/fisiologíaRESUMEN
BACKGROUND: Hematological side effects are not generally expected due to radiotherapy involving limited radiation fields; however, patients with squamous cell carcinoma of the head and neck (SCCH and N) receiving radiation therapy frequently have chronic intraoral infections. Xerostomia has been implicated as a cause of it, but local or systemic immune alterations are not usually considered. METHODS: With the purpose of evaluating the impact of radiotherapy treatment to different anatomic sites on immune function, 70 patients were evaluated during and after radiotherapy: 50 cases with SCCH and N, 10 with squamous cell carcinoma of the uterine cervix (SCCUC) and 10 patients with central nervous system tumors (CNS). We analyzed lymphocyte counts and T-cell subsets, and over time, their association with the presence of intracellular infections and disease-free survival. RESULTS: Severe lymphopenia was observed in patients with SCCUC and SCCH and N by the fifth week of treatment. Patients with CNS tumors developed mild lymphopenia. In patients with SCCH and N and UC, lower counts were seen in B cells and total T lymphocyte counts including both CD4(+) and CD8(+) cell subsets. The patients with SCCUC recovered lymphocyte counts by the 24th month but T-cell subsets lagged behind. None of the SCCH and N patients had fully recovered by 60 months of follow-up. Recurrence correlates with low lymphocyte counts. DISCUSSION: This work highlights the vulnerability of the head and neck area to the impact of radiotherapy as a reservoir of lymphoid cells. The possibility of recovery as a consequence of thymopoiesis and/or peripheral clonal expansion may limit the antigen-specific recognition of relevant tumor or microbial antigens and cause significant and prolonged immune alterations that may impact long-term survival.