Tertiary lymphoid structures in anticancer immunity.

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment. TLS have also garnered considerable interest as a predictive biomarker of the response to antitumour therapies, including immune checkpoint blockade and, possibly, chemotherapy. However, several important questions still remain regarding the definition of TLS in terms of both their cellular composition and functions. Here, we summarize the current views on the composition of TLS at different stages of their development. We also discuss the role of B cells and T cells associated with TLS and their dialogue in mounting antibody and cellular antitumour responses, as well as some of the various mechanisms that negatively regulate antitumour activity of TLS. The prognostic value of TLS to the clinical outcome of patients with cancer and the relationship between TLS and the response to therapy are then addressed. Finally, we present some preclinical evidence that favours the idea that manipulating the formation and function of TLS could lead to a potent next-generation cancer immunotherapy.

[Oncolytic viruses: Actors and deliverers of therapeutic proteins against tumors]. / Les virus oncolytiques : acteurs et vecteurs de protéines thérapeutiques contre les tumeurs.

The discovery of the unique ability of certain viruses to specifically target cancer cells has led to significant advancements in cancer immunotherapy research. In addition to inducing specific lysis of cancer cells, oncolytic viruses (OV) have been genetically modified to express molecules of interest within the tumor bed. The use of OV as vectors for therapeutic molecules has allowed to enhance antitumor responses while limiting the adverse effects associated with systemic administration of the molecule. Other studies are currently focused on delaying the neutralization and clearance of the virus by the host's immune system and improving its delivery insight tumors.

Title: Les virus oncolytiques : acteurs et vecteurs de protéines thérapeutiques contre les tumeurs. Abstract: La mise en évidence de la capacité unique de certains virus à cibler spécifiquement les cellules cancéreuses a ouvert de nouvelles perspectives pour la recherche en immunothérapie des cancers. Outre leur capacité à induire la destruction spécifique des cellules cancéreuses, les virus oncolytiques (OV) ont été modifiés génétiquement pour exprimer des molécules thérapeutiques directement au sein de la tumeur. L'utilisation des OV comme vecteurs de molécules thérapeutiques a permis d'augmenter les réponses anti-tumorales, tout en limitant les effets indésirables liés à une administration par voie générale de ces molécules. D'autres recherches visent aujourd'hui à limiter la neutralisation et l'élimination du virus par le système immunitaire de l'hôte et à améliorer son accès aux tumeurs.

Harnessing the power of oncolytic virotherapy and tertiary lymphoid structures to amplify antitumor immune responses in cancer patients.

Tertiary lymphoid structures (TLS) are ectopic aggregates of immune cells that develop in non-lymphoid tissues under persistent inflammation. Since their presence has been associated with a better prognosis in cancer patients, modulating TLS formation is being part of new challenges in immunotherapy. Although mechanisms underlying TLS genesis are still not fully understood, different strategies have been developed in preclinical models to induce their formation and ultimately enhance antitumor responses. Herein, we will discuss a new approach that would consist in using oncolytic viruses (OV). These viruses have the unique feature to preferentially infect, replicate in and kill cancer cells. Their immunoadjuvant property, their use as a vector of therapeutic molecules and their selectivity for cancer cells, make them an attractive strategy to induce TLS in the tumor microenvironment. This review will examine the current knowledge about TLS neogenesis, approaches for inducing them, and relevance of using OV for this purpose, especially in combination with immunotherapy such as immune checkpoint blockade.