Immunomodulation of the Tumor Microenvironment: Turn Foe Into Friend

Abstract

Immunotherapy, where the patient's own immune system is exploited to eliminate tumor cells, has become one of the most prominent new cancer treatment options in the last decade. The main hurdle for classical cancer vaccines is the need to identify tumor- and patient specific antigens to include in the vaccine. Therefore, in situ vaccination represents an alternative and promising approach. This type of immunotherapy involves the direct intratumoral administration of different immunomodulatory agents and uses the tumor itself as the source of antigen. The ultimate aim is to convert an immunodormant tumor microenvironment into an immunostimulatory one, enabling the immune system to eradicate all tumor lesions in the body. In this review we will give an overview of different strategies, which can be exploited for the immunomodulation of the tumor microenvironment and their emerging role in the treatment of cancer patients.

Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma

“…Systemic administration of mCelyvir was followed by changes in the TME, more remarkable in the spontaneous model than the induced one. After treatment, TME showed a less pro-tumoral and more inflammatory profile, a scenario that contributes to create a more proimmune local situation for an antitumor immune response, as has been previously described [33,34]. Today it is well accepted the immunomodulatory role associated to oncolytic virotherapy through several secondary mechanisms derived from the tumor cell infection itself [6].…”

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

“…Several studies have reported that the effectiveness of immunotherapies depends on reactivating the host immune response of the tumor immune microenvironment (TME) . However, the TME, which comprises immune cells, vessel cells, fibroblasts, and the extracellular matrix, is diverse across tumor patients, and different TME patterns can drive wither tumor repression or progression . As described in a previous study, patients with a “hot” or highly infiltrated TME have more preexisting immune reserves, suggesting that ICI‐based monotherapy will likely be effective for these patients, but patients with a “cold” or non‐infiltrated TME always lack preexisting immune reserves, indicating that ICIs alone will not be sufficient .…”

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

“…For response strati cation and ideal patient selection, it is necessary to detect the tumor PD-L1 expression level. It is worth noting that the tumor cells are surrounded by a homeostatic and dynamic TME that involves many uncertain factors including cytokines secretion, hypoxia, in ammation and treatment responses, and changes in one of these factors affects tumor PD-L1 expression [14]. Hence, it is suspicious to determine PD-L1 expression on tissue samples by immunohistochemical (IHC) analysis, and a more effective PD-L1 detection method is urgently required.…”