Tumorigenesis is related to the generation of heterogeneous tumor cell population, which is the result of genetic and epigenetic alterations followed by clonal selections and subsequent expansion. In basic studies genetic, histological and morphological diversity of different clones within a patient's neoplasm and specifics of their interrelation with patient's immune system are investigated mostly on the models of tumors of epithelial origin. Mesenchymal tumors such as soft tissue and bone-derived sarcomas (STBS) have been poorly studied in this regard. The molecular genetic methods used to examine intratumoral heterogeneity do not currently provide insight into which portion of the identified subclones are able to grow autonomously. Limiting dilution cloning demonstrates the existence of self-regulating tumor cells in the population and can serve as an independent prognostic predictor of poor prognosis.

Intratumoral heterogeneity results not only in differences in growth dynamics, gene expression, and phenotypic markers, but also in the resistance to treatment, especially immunotherapy, thus causing tumor eluding immune escape. The changes that accompany this process can be affected by the cellular immune system, resulting in an imbalance between populations. The variations in the population composition of immune system cells are now widely debated as a predictor of response to immunotherapy, which is of obvious interest for sarcomas, where the effectiveness of chemotherapy is low and the prognosis is unfavorable, especially in case of metastatic disease development. The search for new predictive markers of disease prognosis and treatment efficacy is an important task, to which this study is focused. Our results demonstrate that clonogenic tumor characteristics such as clonogenic potential is independent predictor of unfavorable prognosis in cases of cancer and correlate with the clinical characteristics of the tumor such as overall survival (OS) and progression free survival (PFS). It was found that patients with clonogenic sarcomas had a lower content of activated cytotoxic T-lymphocytes (CTL) with the CD3⁺CD8⁺HLA^-DR⁺ phenotype and an increased number of natural NK killers (p < 0.05) compared to nonclonogenic tumors. In addition, according to our data, a high neutrophil to lymphocyte ratio (NLR), a low value of major T-lymphocyte populations, and a higher number of natural killer cells (NK) in the blood can be negative prognostic factors for the immunotherapy of this disease.

肿瘤发生与异质肿瘤细胞群的产生有关，这是遗传和表观遗传改变以及随后的克隆选择和随后的扩增的结果。在基础研究中，患者肿瘤内不同克隆的遗传、组织学和形态学多样性以及它们与患者免疫系统的相互关系的细节主要在上皮来源的肿瘤模型上进行研究。在这方面，对间充质肿瘤如软组织和骨源性肉瘤 (STBS) 的研究很少。用于检查肿瘤内异质性的分子遗传学方法目前无法深入了解已识别的亚克隆的哪一部分能够自主生长。

肿瘤内异质性不仅导致生长动力学、基因表达和表型标志物的差异，还导致对治疗特别是免疫治疗的抵抗，从而导致肿瘤逃避免疫逃逸。伴随这一过程的变化可能会受到细胞免疫系统的影响，从而导致群体之间的不平衡。免疫系统细胞群体组成的变化现在被广泛争论为免疫治疗反应的预测因子，这对肉瘤具有明显的意义，因为化疗的有效性低且预后不良，尤其是在转移性疾病发展的情况下. 寻找疾病预后和治疗效果的新预测标志物是本研究重点关注的一项重要任务。我们的研究结果表明，克隆形成性肿瘤特征（如克隆形成潜力）是癌症病例预后不良的独立预测因子，并且与肿瘤的临床特征（如总生存期 (OS) 和无进展生存期 (PFS)）相关。结果发现，克隆性肉瘤患者的活化细胞毒性 T 淋巴细胞 (CTL) 含量较低，CD3⁺ CD8 ⁺ HLA ^- DR ⁺表型和与非克隆性肿瘤相比增加的天然 NK 杀伤因子 (p < 0.05)。此外，根据我们的数据，中性粒细胞与淋巴细胞的比率 (NLR) 高、主要 T 淋巴细胞群的值低以及血液中自然杀伤细胞 (NK) 的数量较多可能是免疫治疗的不良预后因素这种病的。