Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists.

Mesenchymal stem cells (MSCs) are recognized for their immunomodulatory capabilities, tumor-homing abilities, and capacity to serve as carriers for therapeutic agents. This review delves into the role of adoptively transferred MSCs in tumor progression, their interactions with the tumor microenvironment, and their use in delivering anti-cancer drugs, oncolytic viruses, and genetic material. It also addresses the challenges and limitations associated with MSC therapy, such as variability in MSC preparations and potential tumorigenic effects emphasizing the need for advanced genetic engineering and personalized approaches to enhance therapeutic efficacy.

Targeting immunogenic cell stress and death for cancer therapy.

Immunogenic cell death (ICD), which results from insufficient cellular adaptation to specific stressors, occupies a central position in the development of novel anticancer treatments. Several therapeutic strategies to elicit ICD - either as standalone approaches or as means to convert immunologically cold tumours that are insensitive to immunotherapy into hot and immunotherapy-sensitive lesions - are being actively pursued. However, the development of ICD-inducing treatments is hindered by various obstacles.

Shifting the paradigm: engaging multicellular networks for cancer therapy.

Most anti-cancer modalities are designed to directly kill cancer cells deploying mechanisms of action (MOAs) centered on the presence of a precise target on cancer cells. The efficacy of these approaches is limited because the rapidly evolving genetics of neoplasia swiftly circumvents the MOA generating therapy-resistant cancer cell clones. Other modalities engage endogenous anti-cancer mechanisms by activating the multi-cellular network (MCN) surrounding neoplastic cells in the tumor microenvironment (TME).

Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma.

The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel (P = 0.