Carcinogenesis has been associated with genetic mutations, DNA damage, infections, and exposure to radiation and other toxic chemicals. The overall mortality rate for cancer has declined due to the continued efforts of researchers for finding diagnostic and therapeutic markers as well as relevant medications and therapies. The heterogeneity of tumors and the tumor microenvironment is very useful for cancer diagnosis, treatment, and prognosis. The tumor microenvironment (TME) is a complicated system involving infiltrating immune cells, tumor-related stromal cells, endothelial cells, and the extracellular matrix. TME is involved in gene expression and molecular functions of tumor cells, which is closely related to the response to the immunotherapies. Increasing evidence shows that infiltrating immune cells such as T cells, B cells, macrophages, dendritic cells, monocytes, neutrophils, and mast cells can regulate cancer development and progression. Tumor cells in the TME can invade surrounding tissues or metastasize through lymphatic vessels and the blood and the infiltrated cells can stimulate the host’s immune response, releasing cytokines, cytokine receptors, and other factors, which directly or indirectly promote or inhibit tumor cell proliferation.

As such, studying the differential expression of genes and infiltrating cells in different tumors and normal controls has great importance for identifying immune-related prognostic targets. The recent advancements in cancer therapy have improved treatment outcomes by immunotherapy such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell adoptive immunotherapy; a type of treatment in which T cells taken from the patients are modified in the laboratory (adding special targets that bind with specific receptors) so that they attack cancer cells. However, patients with advanced stage or unfavorable malignant tumors still face a poor prognosis and recurrence, and the CAR-T therapy remains limited by the lack of ideal or appropriate targets in solid tumors. Thus, more and more comprehensive studies related to genetic regulation, immune cell infiltration, and immune functions are being carried out to identify the related biomarkers and underlying mechanisms of cancer development and progression, ultimately for use in targeted therapy and immunotherapy.

The aim of the current Special Issue is to collect original research articles and review articles related to cancer development, specifically factors related to the tumor heterogeneity and immune infiltration in the tumor microenvironment, regulation of cancers through immune cells, and immune checkpoint inhibitors.

Potential topics include but are not limited to the following:

• The contribution of tumor heterogeneity to the development and progression of cancers
• The tumor microenvironment as major contributor to cancer progression, diagnosis, treatment, and prognosis
• Regulation of immune cell infiltration in the tumor microenvironment
• The critical role of immune checkpoint inhibitors in treatment and prognosis of cancers
• Mechanism of anti-tumor drugs, specifically the regulation of immune checkpoints
• Transcriptomics and proteomics of the tumor microenvironment
• Metabolic regulation of the tumor microenvironment and immune infiltration