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Immunotherapy has provided a new avenue to treat metastatic cancers, which result in ∼90% of cancer related deaths. However, current immunotherapies, such as immune checkpoint therapy (ICT), have met with limited success, primarily due to tumor intrinsic and extrinsic factors that inhibit antitumor immune responses. To overcome the immune suppression of the tumor microenvironment (TME) and enhance the tumoricidal activity of ICT, phototherapy, particularly photothermal therapy (PTT), combined with nanomedicine has become a viable option. PTT disrupts target tumor homeostasis, releasing tumor associated antigens (TAAs), tumor specific antigens (TSAs), danger associated molecular patterns (DAMPs), and scarce nutrients required to “feed” activated antitumor immune cells. While nanoparticles localize and specify the phototherapeutic effect, they can also be loaded with immune stimulants, TME modulators, and/or chemotherapeutic agents to greatly enhance immune stimulation and tumor killing. Combining these three technologies, which we term nano-ablative immunotherapy (NAIT), with ICT can greatly enhance their therapeutic effects. In this review, we will discuss the successes and limitations of NAIT + ICT. Specifically, we will discuss how the TME limits tumoricidal activity and what should be considered to overcome these limitations.

Nanotechnology, photonics, and immunotherapy are far-reaching technologies with the potential to revolutionize the field of cancer diagnostics and therapeutics. While each technology has limitations in cancer treatment, they can be synergized to exert profound impact on the balance and modulation of immunoediting in tumor microenvironment (TME) and in the entire host immune system. We provide our perspectives on how nano-photo-immuno interactions can be used as an effective therapy, particularly when combined with other treatment modalities, such as checkpoint immune therapy, chemotherapy, and TME modulation, to provide a long-term, tumor-specific immunity against tumor metastasis and tumor recurrence.

N‐dihydrogalactochitosan (GC) is an immune stimulant/adjuvant. Synthesized from chitosan and galactose, GC is a new chemical entity that significantly enhances the immune‐stimulating properties of its parental material, chitosan, making it a promising therapeutic agent. When used in combination with antigenic material, GC stimulates innate and adaptive antitumor and antiviral immunities. However, its mechanism has not been fully investigated. Herein it is demonstrated that GC drives type I IFN activation in antigen‐presenting cells (APCs). More importantly, GC drives alternative STING pathways, leading to inflammatory cell death that enhances dendritic cell (DC) activation. GC‐activated DCs trigger a variety of nucleic acid sensing pattern recognition receptors (PRRs) pathways and IL‐1β production via the activation of the inflammasome. In vivo, GC induces a potent response of type I IFNs and upregulates genes associated with STING signaling within the tumor microenvironment (TME). Moreover, intratumoral delivery of GC reduces the numbers of M2‐like macrophages and increases M1‐like macrophages residing within the TME, while subsequently increasing the number of activated DCs. This findings demonstrate that GC acts as a multimodal immune stimulant via STING to generate a broad type I IFN response. This uniquely broad response holds therapeutic promise in generating enhanced antitumor and antiviral immunities. [ABSTRACT FROM AUTHOR]

The northern part of Zhangqiu district in Jinnan City has developed a thick sedimentary formation from the late Paleozoic to the Cenozoic. In this district, relatively well-developed fault structures and magmatic rocks provide good geothermal conditions. Abundant geothermal resources have been discovered in the study area, with three geothermal wells located near the fault zone. Therefore, establishing the genesis model of geothermal resources is significant for their future sustainable development and utilization. Based on hydrochemical and isotopic data of the study area, hydrochemical characteristics, water-rock interaction process, recharge source and formation age of geothermal water have been analyzed in this study. Besides, the elevation of the recharge area, thermal reservoir temperature, and depth of hot water circulation have also been calculated. Research findings show that geothermal water in the study area is composed of Cl·SO4-Na·Ca or SO4·Cl-Ca·Na, whose hydrochemical components mainly come from water-rock dissolution in the similar hydrogeochemical process. The source of water recharge is supplied by atmospheric precipitation, at an elevation from +563 m to +616 m. The 14C apparent age ranges from 5.55 ka to 29.71 ka. The geothermal water is mixed with modern water and ancient water. The chalcedony temperature scale shows that the temperature of geothermal reservoir is at 41.9-52.4 °, with the circulation depth of geothermal water at 622-1,565 m. The study area is a small-opened karst hot reservoir with deep circulation, during which geothermal water is heated up. Formation and enrichment of geothermal water are significantly controlled by fault structures. The geothermal reservoir is of stratified and banded type, belonging to geothermal resources at medium-low temperature. [ABSTRACT FROM AUTHOR]