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Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.

Many patients fail to respond to EGFR-targeted therapeutics, and personalized diagnostics is needed to identify putative responders. We investigated 1630 colorectal and lung squamous carcinomas and 1357 normal lung and colon samples and observed huge variation in EGFR pathway activation in both cancerous and healthy tissues, irrespectively on EGFR gene mutation status. We investigated whether human blood serum can affect squamous carcinoma cell growth and EGFR drug response. We demonstrate that human serum antagonizes the effects of EGFR-targeted drugs erlotinib and cetuximab on A431 squamous carcinoma cells by increasing IC50 by about 2and 20-fold, respectively. The effects on clonogenicity varied significantly across the individual serum samples in every experiment, with up to 100% differences. EGF concentration could explain many effects of blood serum samples, and EGFR ligands-depleted serum showed lesser effect on drug sensitivity.

Here we present the results of comparative immunoenzyme assay of the initial serum levels of VEGF in breast cancer patients (stages T1N0M0 and T2N0M0) and apparently healthy women (controls). It was found that VEGF concentrations in the serum of patients with breast cancer stages T1N0M0 and T2N0M0 significantly surpassed the control levels. Increased levels of VEGF surpassing the threshold values were more often observed in patients with T2N0M0 breast cancer compared to patients with T1N0M0 tumor. At the same time, this marker cannot be used in the diagnostics of this disease because in only 21.4% patients serum level of VEGF surpassed the upper boundary for this growth factor observed in the serum of control women. Serum concentration of VEGF in patients with stages T1N0M0 and T2N0M0 breast cancer did not depend on patient's age and reproductive function and receptor status of the primary tumor (estrogen and progesterone receptors), but was closely associated with tumor histogenesis and differentiation degree. Significantly higher levels of VEGF were observed in patients with lobular infiltrative breast carcinoma compared to patients with ductal tumors and in patients with low-differentiated tumors compared to highly and moderately differentiated tumors. High initial concentrations of VEGF (>300 pg/ml) were more often detected in patients with T2N0M0 breast cancer developing relapses within the first 3 years of follow-up compared to patients without relapses during the corresponding period (p=0.001). These findings suggest that serum level of VEGF in patients with T2N0M0 breast cancer before treatment can be used as an additional marker in parallel with standard clinical and morphological signs of the disease for more precise prognosis of early relapse (during the first 3 years of follow-up).

Introduction. There is ample evidence that disseminated tumor cells (DTC), which are found in the bone marrow (BM) of patients with breast cancer (BC), including early stages, are progenitors of subsequent distant metastasis. Therefore, BM-DTC represent an additional tool for understanding carcinogenesis and estimating prognosis. Nevertheless, the existing data are controversial. The purpose of the study – to determine the frequency of DTC detection in BM of patients with luminal BC and also its relationship with some clinical and immunophenotypic parameters. Materials and methods. BM bioptates of 65 luminal BC patients were analyzed for the presence of DTC by Attune Acoustic Focusing Cytometer. For the first time in Russia, the sensitivity of the DTC detection method in the BM to the level of 1 × 10–7 myelocaryocytes was increased. Results. In BM, DTC were detected in 40 % of patients, and this finding did not correlate with stage of BC and degree of malignancy. The level of CD8+ lymphocytes in patients with DTC in the BM was significantly lower and amounted to 39,2 % versus 48,1 % in patients without DTC (p = 0,011). The content of myelocaryocytes with DTC-positive status was 1,6 times lower than in the absence of DTC (р = 0,007). Other parameters of the myelogram did not differ significantly. Moreover, no significant correlations were found between the presence of DTC in BM and the breast tumor immunophenotype (HLA-I: p = 0,74; HLA-DR: p = 0,93; CD71: p = 0,46). Conclusion. The presence of BM-DTC is more interrelated with myelogram and subpopulation of BM lymphocytes than with the clinical characteristics of tumor.

The innate immunity system plays an important role in antitumor protection, and more and more attention has been paid to its study recent years. However, the interrelation of the effect or subpopulations of the cells of the innate immunity in bone marrow with clinical parameters is poorly studied. The paper presents data on the composition of innate immune cells in the bone marrow of 64 patients with operable breast cancer, as well as 10 women with benign processes in the mammary gland. As result a significant correlation between the molecular subtype of cancer and the level of B1- lymphocytes was identified. Breast cancer patients levels of NK cells (CD56 + CD3- and CD16 + CD3-) in the bone marrow were significantly higher in patients with low proliferative activity (Ki-67 less than 20%), compared to patients having a high tumor proliferation index. Populations of NK cells were interrelated with erythropoiesis in patients with breast cancer and were significantly higher in cases of reduced basophilic and polychromatophilicnormoblasts.

Currently, mammography is the main screening method for diagnosing breast cancer (BC); but the process of carcinogenesis begins long before the appearance of a visualized tumor. For successful early diagnosis of breast cancer, a systematic approach is required, that includes all stages of tumor development. On the example of BC we consider the possibilities of integrating the recent scientific achievements of oncogenetics and proteomics with standard methods. In this article we investigate the possibilities of using genetic research, serum cancer markers and radiation methods for early diagnosis of BC. This article also presents potential options for managing high-risk development of this disease.