Changes In Tumor Infiltrating Lymphocytes Of Peripheral Blood And Tissue During Chemotherapy In Patients With Gastric Cancer

Abstract

To study the state of systemic immunity and local immunity before and during chemotherapy in patients with gastric adenocarcinoma. From 2017 to 2018 at the Tashkent city branch of the Republican specialized scientific and practical medical center of oncology and radiology 20 primary metastatic patients with gastric adenocarcinoma received chemotherapy. The sampling of biological material (peripheral blood, tumor tissue) was carried out twice (before treatment and during the first control examination, after 3 courses). The percentage of the degree of infiltration of tumor tissue by lymphocytes (CD45+CD14-TILs) was estimated by flow cytometry; T cells (CD3+CD19-TILs); B cells (CD3-CD19+TILs); NK cells (CD3-CD16+CD56+TILs); CD16 and CD8 effector cells and their cytotoxic potential (CTP) (CD16+Perforin+TILs; CD16CTPTILs), (CD8+Perforin+TILs; CD8CTPTILs); regulatory T cells - NKT cells (CD3+CD16+CD56+TILs), CD4 (CD4+CD25+CD127-TILs) and CD8 (CD8+CD11b-CD28-TILs) regulatory cells and these parameters of systemic results. The factor of a favorable prognosis for PFS in patients with metastatic gastric cancer in the peripheral blood was an increase in the number of CD8 + T-regulatory cells (5.1% - 12.1%, p = 0.019), and in tumor tissue - an increase in the perforin potential of effector CD16 cells (0.5% - 4.9%, p = 0.030) and their cytotoxic potential (13.2% - 55.7%, p = 0.011). When assessing the changes in the indices of local immunity during chemotherapy, it was noted a negative effect of an increase of T cells (22.0% - -9.7%, p = 0.012), NKT - cells (207.9% - -13.8%, p = 0.002) and CD4 + T-regulatory cells (190.7% - -25.2%, p = 0.002). In contrast, an increase in the level of effector CD16 cells during chemotherapy increases the likelihood of surviving PFS - 9 months (-69.5% - 9.1%, p = 0.013). Indicators of local and systemic immunity serve as additional prognostic factors for gastric cancer.

Modern View on the Problem of Triple Negative Breast Cancer

“…According to Lin et al ., in patients with triple negative receptor status , metastasis to the visceral organs (lungs and brain) is more often observed in comparison with patients with the ER +/ Her -2/ neu -phenotype, and bones are much less often involved in the process [6,9 ]. A number of studies have shown that a greater risk of relapse in TNR is observed in the first three years after surgery [15], while in patients with tumors with an ER-positive phenotype, local recurrence of the disease is most often observed between 5 and 10 years after surgical treatment [11,12].…”

“…Nonspecific invasive ductal carcinomas account for about 60-75% of all breast cancer cases. Specific types account for 20-25% of all, of which the most common are lobular, tubular, papillary and mucinous tumors [5,12]. Heterogeneity within the same tumor ( intratumoral ) or between morphologically similar tumors of the same type ( intertumoral ) is now well known and accepted.…”

“…-" luminal "differentiates into 2 or 3 subgroups, reflects ER , ER regulatory genes and the expression of genes that are expressed in normal luminal epithelial cells; -" Her 2 positive" reflects amplification and overexpression ErB 2/ Her 2; -"basal" (reflecting ER , PR and Her 2-negative expression of genes expressed in normal basal and/or myoepithelial cells of the breast); These molecular subtypes were formed by differentiating numerous genes and dividing them into clusters to separate them into groups in terms of transcription [ 12 ]. Thus, there are three main subtypes that can be identified using only genes associated with ER and Her 2 phenotypes, rather than using hundreds of intrinsic genes [8,16].…”

“…Thus, based on data from Her 2+ patients who were resistant to treatment with monoclonal antibodies ( Herceptin ) targeting the extracellular domain or who relapsed after treatment, possible causative mechanisms were explored. Part of Her 2+ patients with breast cancer who have a poor prognosis express the heterogeneous group of carboxy-terminal fragments of Her 2 [ 12,16 ]. Similar to histological evaluation, molecular tests are performed that show the average level of gene expression, and also that breast cancer is a heterogeneous disease [ 15,18 ].…”