Characteristics of the parameters of the innate and acquired immune response during the period of adaptation to training at a Medical University

Adaptation for new social conditions is an inevitable factor which the first-year students undergo when entering a medical school. Immune system as a part of entire structural and functional homeostatic complex, is involved into the adaptive reactions, thus pointing to its participation in fitting the new lifestyle among first-year students. One should note some peculiarities of immune reactions which depend on the organization pattern of educational process: despite common features of studies, the training environment for beginners at the military training center (VTC) is different from those for students at the medical and preventive faculty (LPF). The purpose of our study was to compare quantitative and functional parameters of immune system in the first-year students at a medical university, depending on distinct features of educational arrangement.The study included 36 first-year students of the Medical University divided into two groups, comparable for age, sex, and physical condition. The first group included 18 first-year VUTS students, whereas the second group consisted of 18 LPF pupils. Studies of immunological parameters in peripheral blood were carried out three months after the training was started. We have assessed counts and functional potential of T cells, their subpopulation profile, B lymphocyte counts, and serum level of IgA, IgM and IgG, total numbers of natural killer cells and proportion of cytolytically active forms, oxygen-producing activity of neutrophils, and the numbers of peripheral monocytes expressing type 2,4 Toll-like receptors (TLR). Comparison of the adaptive immune response parameters did not reveal any gross differences between the groups. At the same time, evaluation of markers reflecting functional potential of innate immunity cells revealed distinct signs of immune reactions, depending on the faculty of the first-year students. It has been shown that the proportion of functionally active NK-cells containing lytic granzyme B granules was lower in the EUTC students. Also, military medical students have a statistically significantly lower relative and absolute number of peripheral blood monocytes expressing surface TLR 4. The detected signs of suppressed functional potential of macrophages and natural killer cells in the first-year OUV students represent the possibly alarming factor of impaired adaptive reserves of immune system. The data obtained are of interest for development of immune rehabilitation programs to prevent clinical manifestations of immune dysfunction.

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Trial-in-progress: A pilot study of combined immune checkpoint inhibition in combination with ablative therapies in subjects with hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.tps355 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. TPS355-TPS355

Author(s):

Hailey Kathryn Carroll ◽

Umair Aleem ◽

Pooja Varghese ◽

Marie Galligan ◽

Michele Bourke ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Response ◽

Immune System ◽

Pilot Study ◽

Natural Killer Cells ◽

Natural Killer ◽

Immune Checkpoint ◽

Innate Immune System ◽

Innate Immune

TPS355 Background: Locoregional therapies for hepatocellular carcinoma, such as transcatheter arterial chemoembolization (TACE) or ablation, can induce a peripheral anti-tumor immune response. This may be amplified by immune checkpoint inhibitors (ICI). Early and higher anti-CTLA4 dosing could potentially lead to better priming and a stronger immune response. Recent data has suggested that early (day 1 only), increased doses of anti-CTLA4 therapy, was associated with encouraging clinical activity and a tolerable safety profile. This study will evaluate dual immune checkpoint, CTLA4 (tremelimumab, day 1-only dosing) and PD-L1 (durvalumab) blockade in combination with TACE in patients with advanced HCC. Intensive peripheral immune-monitoring and longitudinal on-treatment tumor biopsies will focus on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses. Methods: Patients with HCC (Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1; sorafenib-naïve or experienced) are being enrolled in a pilot study (Study Number UCDCRC/19/01) of tremelimumab at 2 dose levels (DL1 and DL2) in combination with durvalumab and TACE until disease progression (per irRECIST). DL1: tremelimumab (75mg q28 days for 4 doses) and durvalumab (1500mg q28 days). DL2: tremelimumab (300mg in a single dose on day 1) and durvalumab (1500mg q28 days). Subtotal TACE will be performed during study week 6 with the dose-limiting toxicity (DLT) evaluation period encompassing the first 8 weeks of the study. Primary endpoint is 6-month progression-free survival with secondary efficacy endpoints being safety, tolerability and overall survival. Exploratory objectives will evaluate changes in immune parameters in the tumor and peripheral blood of patients undergoing anti-CTLA4 therapy pre- and post-RFA or TACE. A major focus will be on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses. Patients will be enrolled and treated at St Vincent’s University Hospital in Dublin, Ireland. This study is currently open and actively recruiting. Clinical trial information: EudraCT Number 2019-002767-98.

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