Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways

Abstract

Despite the broad application of different immunotherapeutic strategies for the treatment of solid as well as hematopoietic cancers, the efficacy of these therapies is still limited, with only a minority of patients having a long-term benefit resulting in an improved survival rate. In order to increase the response rates of patients to the currently available immunotherapies, a better understanding of the molecular mechanisms underlying the intrinsic and/or extrinsic resistance to treatment is required. There exist increasing evidences that activation of different oncogenic pathways as well as inactivation of tumor suppressor genes (TSG) in tumor cells inhibit the immune cell recognition and influegnce the composition of the tumor microenvironment (TME), thus leading to an impaired anti-tumoral immune response. A deeper understanding of the link between the tumor milieu and genomic alterations of TSGs and oncogenes is indispensable for the optimization of immunotherapies and to predict the patients’ response to these treatments. This review summarizes the role of different cancer-related, oncogene- and TSG-controlled pathways in the context of anti-tumoral immunity and response to different immunotherapies.

A novel immune-nutritional score predicts response to neoadjuvant immunochemotherapy after minimally invasive esophagectomy for esophageal squamous cell carcinoma

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Prognostic Value of Combined LMR and CEA Dynamic Monitoring in Postoperative Colorectal Cancer Patients

“… 21 , 22 Lymphocytes have an anti-tumor effect by producing high levels of anti-tumor cytokines and cytotoxic molecules, inhibiting different oncogenic pathways (angiogenesis, epithelial-mesenchymal transition), and promoting apoptosis of tumor cells. 23 , 24 However, the anti-tumor immune response of lymphocytes is negatively regulated by tumor cells and stromal cells such as M2-type TAM and tumor-associated fibroblasts. 24 Inhibiting TAM activation to M2 type can increase the number of CD8+ T cells, enhance anti-tumor efficacy, and reshape the TME.…”

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

“…While these humoral and cellular immunotherapy options are highly efficient in B-cell leukemias, their application is limited for the treatment of solid tumors which may be due to mechanical barriers, the lack of expression of suitable homing receptors and adhesion molecules which interferes with an efficient infiltration of immune cells into tumor tissues. Moreover, the immunosuppressive tumor microenvironment including the expression of check point inhibitors leads to a downregulation of infiltrated immune effector cells (e.g., [ 11 , 12 , 13 ]).…”