Immunomodulation in cancer.

We have to strengthen our 'chess-playing skills' when using immunotherapeutic approaches in cancer treatment: know the cancerous opponent, study its evolution and have an eye for its weaknesses. Besides tumor cells, other pieces on the board are stromal cells, endothelial cells and different immune cells. Some of these immune cells, like helper and cytotoxic T cells, natural killer (T) cells and mature dendritic cells are of help, others like regulatory T cells and myeloid-derived suppressor cells belong to the opponent, while macrophages and neutrophils can belong to both. A personalized approach, by selecting the optimal treatment from the myriad of possibilities based on biomarker findings, is essential to attack that particular cancer at that moment. We have to adapt the strategy to the changing positions created by the opponent. Using all these skills, we might control cancer growth in the future.

Hegmans JP ，Aerts JG 《-》

Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents.

The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy. Although largely neglected in the clinical practice, accumulating evidence indicates that the efficacy of conventional and targeted anticancer agents does not only involve direct cytostatic/cytotoxic effects, but also relies on the (re)activation of tumor-targeting immune responses. Chemotherapy can promote such responses by increasing the immunogenicity of malignant cells, or by inhibiting immunosuppressive circuitries that are established by developing neoplasms. These immunological "side" effects of chemotherapy are desirable, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy.

Galluzzi L ，Buqué A ，Kepp O ，Zitvogel L ，Kroemer G ... -  《-》

Non-steroidal anti-inflammatory drugs, tumour immunity and immunotherapy.

Non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable importance in cancer chemoprevention over the last few years. They are now being considered as prospective candidates in cancer immunotherapy because of their striking immune-enhancing impact on various effector elements of anti-tumour immunity on one hand, and to augment the efficacy of different anti-cancer immunotherapeutic strategies on the other. This review specifically discusses the role of NSAIDs in anti-tumour immunity by describing their immunomodulatory effects on different immune cells including tumour-associated macrophages (TAM), dendritic cells (DC), natural killer (NK) cells, T effector cells, and T regulatory cells (Treg). Secondly, the therapeutic perspective of NSAIDs in combination with different anti-cancer immunotherapeutic approaches, in particular the cancer vaccines, tumour-specific monoclonal antibodies, and cytokine-based therapy, has been outlined. At the end, the impact of anti-inflammatories other than NSAIDs on tumour immunity and immunotherapy, and the immunopharmacological potential of selective E-prostanoid (EP) receptor antagonists with respect to cancer immunity have also been discussed briefly.

Hussain M ，Javeed A ，Ashraf M ，Al-Zaubai N ，Stewart A ，Mukhtar MM ... -  《-》

Prevailing over T cell exhaustion: New developments in the immunotherapy of pancreatic cancer.

Pancreatic cancer is one of the most aggressive malignancies and has been considered poorly immunogenic for decades. However, this characterization might be over-simplistic. A more sophisticated approach is needed in order to develop new treatment strategies. In this review, we will focus on T cell exhaustion as a phenomenon of immune failure that is a useful paradigm to characterize immunosuppressive effects. Cancer creates an environment of constant antigen exposure and inflammation. In this setting, T cells transform into a differentiation state that has been termed T cell exhaustion, which is characterized by upregulation of inhibitory receptors, resulting in loss of effector function. The discovery of receptor-mediated immune checkpoints, which prevent uncontrolled T cell reactions, led to the development of a new class of antibodies termed checkpoint inhibitors. Unprecedented results in patients with metastatic melanoma and lung cancer have renewed interest in the immunotherapy of other solid tumor entities, including pancreatic cancer. Data on the efficacy of checkpoint inhibitors in pancreatic cancer are still sparse and indicate limited efficacy as single agents. Combination of checkpoint inhibitors with other immune-activating strategies or cytotoxic drugs might be a way to overcome therapy resistance in the treatment of pancreatic cancer.

Bauer C ，Kühnemuth B ，Duewell P ，Ormanns S ，Gress T ，Schnurr M ... -  《-》

Immunotherapy of cancer: targeting cancer during active disease or during dormancy?

Shah SA ，Zarei M ，Manjili SH ，Guruli G ，Wang XY ，Manjili MH ... -  《-》