Intratumoral immunotherapy: local treatment of a recognized tumor to enhance systemic antitumor immunity

In this century, cancer immunotherapy has become an established treatment modality widely used alongside surgery, radiation, and chemotherapy. However, current approved immunotherapies for solid tumors, most notably checkpoint blockade antibodies, still benefit fewer than 25% of treated patients, and many patients remain ineligible for treatment. A primary reason immunotherapy fails is that tumors generate immune-suppressing mechanisms that shield them from the immune system, meaning any effective immunotherapy must overcome these immunosuppressive signals. Intratumoral immunotherapy (ITIT)—the direct treatment of recognized tumors with immune-stimulating reagents or physical treatments—represents an area of major potential. By targeting tumors locally, ITIT aims to reverse tumor-mediated immune suppression, stimulate robust immune attack, and expand effector and memory T cell populations capable of circulating and controlling metastatic disease. This Research Topic seeks to advance the understanding and clinical translation of ITIT strategies.This Research Topic focuses on intratumoral immunotherapy (ITIT) approaches for solid tumors, encompassing both experimental data and conceptual frameworks. There are many possible approaches to ITIT, and they can be combined with one another or with other local (surgery, radiation) or systemic (checkpoint blockade antibodies, chemotherapy) therapies, further multiplying therapeutic options. The current research challenge lies in identifying the optimal strategies for a given tumor type, particularly those that generate robust systemic antitumor immunity to suppress metastatic disease.Contributors are invited to address themes including: novel ITIT agents and delivery methods; mechanisms of tumor-mediated immune suppression and strategies to overcome them; combination approaches integrating ITIT with local or systemic therapies; preclinical and clinical evidence of abscopal or systemic immune responses following ITIT; and translational strategies for advancing promising ITIT approaches toward clinical application.Current immunotherapies for solid tumors remain effective in only a minority of patients, underscoring the need for new therapeutic strategies. ITIT offers a promising approach by directly targeting tumors with immune-stimulating agents or physical treatments to reverse local immune suppression and generate systemic antitumor responses. However, the diversity of possible ITIT approaches—and their potential combinations with one another and with conventional therapies—presents a significant challenge in identifying the most effective strategies for specific tumor types. This Research Topic serves as a forum for presenting data on ITIT experiments and discussing ITIT concepts to help identify and demonstrate the best therapeutic options and accelerate their translation to the clinic. By bringing together preclinical findings, clinical observations, and mechanistic insights, this Research Topic aims to clarify which ITIT strategies most effectively generate durable systemic immunity against metastatic disease, ultimately guiding the development of optimized, combinatorial treatment regimens.This Research Topic accepts submissions in the following formats: Brief Research Report, Case Report, Classification, Clinical Trial, Editorial, FAIR² Data, General Commentary, Hypothesis and Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Study Protocol, Systematic Review, and Technology and Code. All published articles will undergo rigorous external peer review and may be subject to publication fees.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Manuscripts focusing solely on cost-effectiveness studies are also not considered for publication in this journal.Topic Editor Steven Fiering declares he is an owner of stock in PlantiosX, an early stage biotech. Topic editors: Steven Fiering, Bin Liu Source: https://www.frontiersin.org/research-topics/81259/intratumoral-immunotherapy-local-treatment-of-a-recognized-tumor-to-enhance-systemic-antitumor-immunity