Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy
Sacha GnjaticVincenzo BronteLaura Rosa BrunetMarcus O. ButlerMary L. DisisJérôme GalonLeif HåkanssonBrent A. HanksVaios KaranikasSamir N. KhleifJohn M. KirkwoodLance D. MillerDolores J. SchendelIsabelle TanneauJon M. WiggintonLisa H. Butterfield
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Abstract:
As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.Keywords:
Cancer Immunotherapy
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Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3’s role in TME to its potential as a target in cancer immunotherapy.
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Abstract Background Recently, cancer immunotherapy has become standard for cancer treatment. Immunotherapy not only treats primary tumors, but also prevents metastasis and recurrence, representing a major advantage over conventional cancer treatments. However, existing cancer immunotherapies have limited clinical benefits because cancer antigens are often not effectively delivered to immune cells. Furthermore, unlike lymphoma, solid tumors evade anti-cancer immunity by forming an immune-suppressive tumor microenvironment (TME). One approach for overcoming these limitations of cancer immunotherapy involves nanoparticles based on biomaterials. Main body Here, we review in detail recent trends in the use of nanoparticles in cancer immunotherapy. First, to illustrate the unmet needs for nanoparticles in this field, we describe the mechanisms underlying cancer immunotherapy. We then explain the role of nanoparticles in the delivery of cancer antigens and adjuvants. Next, we discuss how nanoparticles can be helpful within the immune-suppressive TME. Finally, we summarize current and future uses of nanoparticles with image-guided interventional techniques in cancer immunotherapy. Conclusion Recently developed approaches for using nanoparticles in cancer immunotherapy have enormous potential for improving cancer treatment. Cancer immunotherapy based on nanoparticles is anticipated not only to overcome the limitations of existing immunotherapy, but also to generate synergistic effects via cooperation between nanoparticles and immune cells.
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Cancer immunotherapy has shown impressive anti-tumor activity in patients with advanced and early-stage malignant tumors, thus improving long-term survival. However, current cancer immunotherapy is limited by barriers such as low tumor specificity, poor response rate, and systemic toxicities, which result in the development of primary, adaptive, or acquired resistance. Immunotherapy resistance has complex mechanisms that depend on the interaction between tumor cells and the tumor microenvironment (TME). Therefore, targeting TME has recently received attention as a feasibility strategy for re-sensitizing resistant neoplastic niches to existing cancer immunotherapy. With the development of nanotechnology, nanoplatforms possess outstanding features, including high loading capacity, tunable porosity, and specific targeting to the desired locus. Therefore, nanoplatforms can significantly improve the effectiveness of immunotherapy while reducing its toxic and side effects on non-target cells that receive intense attention in cancer immunotherapy. This review explores the mechanisms of tumor microenvironment reprogramming in immunotherapy resistance, including TAMs, CAFs, vasculature, and hypoxia. We also examined whether the application of nano-drugs combined with current regimens is improving immunotherapy clinical outcomes in solid tumors.
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Modulation of the tumor microenvironment is becoming an increasingly popular research topic in the field of immunotherapy, and studies regarding immune checkpoint blockades and cancer immunotherapy have pushed cancer immunotherapy to a climax. Simultaneously, the manipulation of the immune regulatory pathway can create an effective immunotherapy strategy; however, the tumor microenvironment serves an important role in suppressing the antitumor immunity by its significant heterogeneity. A number of patients with cancer do not have a good response to monotherapy approaches; therefore, combination strategies are required to achieve optimal therapeutic benefits. Targeting the tumor microenvironment may provide a novel strategy for immunotherapy, break down the resistance of conventional cancer therapy and produce the foundation for personalized precision medicine. The present review summarized the research regarding cancer immunotherapy from the perspective of how the tumor microenvironment affects the immune response, with the aim of proposing a novel strategy for cancer immunotherapy and combination therapy.
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In the last few decades, cancer immunotherapy becomes an important tactic for cancer treatment. However, some immunotherapy shows certain limitations including poor therapeutic targeting and unwanted side effects that hinder its use in clinics. Recently, several researchers are exploring an alternative methodology to overcome the above limitations. One of the emerging tracks in this field area is nano-immunotherapy which has gone through rapid progress and revealed considerable potentials to solve limitations related to immunotherapy. Targeted and stimuli-sensitive biocompatible nanoparticles (NPs) can be synthesized to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity and to enhance the survival rate of cancer patients. In this review, we have discussed cancer immunotherapy and the application of NPs in cancer immunotherapy, as a carrier of immunotherapeutic agents and as a direct immunomodulator.
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Nanoscience has long been lauded as a method through which tumor-associated barriers could be overcome. As successful as cancer immunotherapy has been, limitations associated with the tumor microenvironment or side effects of systemic treatment have become more apparent. In this Review, we seek to lay out the therapeutic challenges associated with the tumor microenvironment and the ways in which nanoscience is being applied to remodel the tumor microenvironment and increase the susceptibility of many cancer types to immunotherapy. We detail the nanomedicines on the cutting edge of cancer immunotherapy and how their interactions with the tumor microenvironment make them more effective than systemically administered immunotherapies.
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Abstract Background: The tumor microenvironment (TME) has achieved remarkable results in the research of cancer progression in the past few years. it is crucial to understand the nature and function of TME in tumors because of precise treatment strategies for individual cancers having received widespread attention, including immunotherapy. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research is to analyses tumor immune cell infiltration (ICI) in the microenvironment of NB. Methods: We applied CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected and ICI scores were acquired. Subgroups with high ICI scores based on immune activation signaling pathways have better overall survival. Results: The genes of immunosuppressive glycosaminoglycan biosynthesis heparan sulfate signaling pathway were markedly enriched in the low ICI score subgroup. It was inferred that compared with low ICI NB subtypes, patients with high ICI NB subtypes were more likely to respond to immunotherapy and a better prognosis. Conclusion: Notably, our ICI scores not only provided new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment, but also aided new ideas for the development of new NB precision immunotherapy methods.
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Tumor immunotherapy is considered to be a novel and promising therapy for tumors and it has recently become a hot research topic. The clinical success of tumor immunotherapy has been notable, but it has been less than totally satisfactory because tumor immunotherapy has performed poorly in numerous patients although it has shown appreciable efficacy in some patients. A minority of patients demonstrate durable responses but the majority of patients do not respond to tumor immunotherapy as the tumor immune microenvironment is different in different patients for different tumor types. The success of tumor immunotherapy may be affected by the heterogeneity of the tumor immune microenvironment and its components, as these vary widely during neoplastic progression. The deepening of research and the development of technology have improved our understanding of the complexity and heterogeneity of the tumor immune microenvironment and its components, and their effects on response to tumor immunotherapy. Therefore, investigating the tumor immune microenvironment and its components and elucidating their association with tumor immunotherapy should improve the ability to study, predict and guide immunotherapeutic responsiveness, and uncover new therapeutic targets.
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