The tumor microenvironment is a complex network of various interactions between immune cells and non-cellular components such as the extracellular matrix, exosomes and interleukins. Moreover, tumor heterogeneity and its constant modification may alter the immunophenotype and become responsible for its resistance regarding the therapies applied However, it should be remembered that in a strongly immunosuppressive neoplastic microenvironment, the immune system cells undergo reprogramming and most often cease to fulfill their original function. Therefore, understanding what happens within the tumor microenvironment, and which mechanisms are responsible for tumor development and progression should let us know how cancer could protect itself against the immune system. The presented review summarizes the latest information on the interactions between the tumor microenvironment and the cellular and non-cellular components, as well as their impact on cancer development, progression and immune system exhaustion.

Introduction: Detection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, are limited.Material and methods: We examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age 66 years). DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues using a Qiagen QIAamp DNA FFPE-kit. Analysis of mutations was carried out using the KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) with the Cobas 480 realtime PCR apparatus (Roche Diagnostics).Results: KRAS mutations were detected in 190 patients (38%), NRAS mutations in 20 patients (4%), and BRAF mutations in 24 patients (4.8%). There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF gene mutations. These mutations were significantly more often diagnosed in women (55.5%) than in men (41%, p < 0.005). Tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations.Conclusions: Our study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.

The last century was full of numerous scientific discoveries that allowed us to understand the operation and functioning of one of the most complex human systems, i.e. the immune system. One of the most important discoveries was the work of prof. James Alison and Prof. Tasuko Honjo on the development of anti-cancer therapy by inhibiting negative immune regulation (PD-1 and CTLA-4 molecules). Knowledge of the action of these molecules and their huge role in inhibiting the activity of the immune system, e.g. during the developing cancer, created the basis for the development of specific monoclonal antibodies, without which clinicians of many specialties cannot imagine modern cancer therapies. However, the side effects of the therapies used are still quite troublesome, as they can even lead to the death of the patient. In order to minimize the side effects, it would be necessary to reduce the dose, but still maintain the effective level of anticancer activity of the cells of the immune system. In the presented study, 24-hour cultures of PBMC isolated from peripheral blood and bronchoaspirate with various concentrations of nivolumab or atezolizumab were performed. The expression results of the individual activation markers on cultured cells were compared to the expression of these markers on cells not subjected to cell culture. The results of the research work may indicate that individualized dosage of anti-PD-1 and anti-PD-L1 antibodies may in the future contribute to the effective activation of the immune system cells while minimizing the side effects of the therapy.