e14601 Background: Adoptive cell therapies (ACT), including TCR- and CAR-engineered T cells, have demonstrated durable clinical benefit in hematologic malignancies but have shown limited efficacy in solid tumors due to poor T cell infiltration, functional suppression, and early exhaustion within the tumor microenvironment (TME). Strategies to remodel the TME and support T cell function are therefore a major clinical priority. Activation of the stimulator of interferon genes (STING) pathway can induce antitumor inflammation and innate immune activation; however, clinical translation of STING agonists has been limited by poor tumor accumulation and dose-limiting systemic toxicity, often requiring intratumoral administration. We hypothesized that systemic, yet tumor-enriched STING activation could safely reprogram the TME and enhance the therapeutic efficacy of ACT in solid tumors. Methods: We developed an albumin-hitchhiking nanobody–STING agonist (AHNSA) platform designed to exert significantly more effects in the TME. AHNSA was evaluated as an adjuvant to ACT in a TCR-transgenic OT-I T cell transfer model using MC38-OVA tumors. Antitumor efficacy and survival were assessed by tumor volume measurements and Kaplan-Meier survival analyses. Tumor-infiltrating immune populations and transferred T cells were analyzed by flow cytometry and immunohistochemistry to evaluate innate immune activation, T cell infiltration, proliferation, functional state, and expression of exhaustion-associated markers, as well as global changes in TME composition. Results: Systemic administration of AHNSA following ACT resulted in significantly improved tumor control and survival compared with ACT alone. AHNSA treatment increased intratumoral accumulation of dendritic cells and inflammatory macrophages, consistent with STING-mediated innate immune activation, and significantly enhanced infiltration of adoptively transferred T cells. Transferred T cells exhibited increased activation and proliferation with reduced expression of exhaustion markers (PD1, LAG3), indicating improved functional persistence. Immune profiling revealed a coordinated shift toward a pro-inflammatory TME, including enrichment of CD8⁺ T cells and antigen-presenting cells and depletion of immunosuppressive populations such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Conclusions: Targeted systemic STING agonism using an albumin-hitchhiking nanobody platform overcomes key delivery and toxicity barriers associated with STING activation and potently enhances adoptive T cell therapy by reprogramming the solid tumor microenvironment. These findings support a clinically relevant combination strategy to improve the efficacy of cellular immunotherapies in solid tumors and provide a strong rationale for translational development.

Abstract Introduction Heat is a cardinal feature of inflammation that is also generated by many solid tumors. We have recently shown that heat promotes Th1-mediated inflammation via cGAS/STING activation, and also decreases suppressive capacity of regulatory T cells (Tregs) with no detectable STING activation. The cGAS/STING pathway detects cytosolic nucleic acids, inducing Type I Interferon (IFN-I) production and stimulating T cell immunity when activated in innate cells. It is also highly expressed in T cells, yet the CD4+ T cell-intrinsic effects of STING remain underexplored, and are especially unclear within regulatory T cells. Methods Given the pro-inflammatory effects of heat, and the likelihood that Tregs are exposed to heat while suppressing inflammation, we explored the effects of STING and heat (39 °C) on induced Tregs (iTregs) compared to Th1 cells. Results Notably, we have found that STING activation reprograms iTregs into IFN-I-producing T helper-like cells with inflammatory function accompanied by decreased oxidative metabolism and suppressive function. Both heat and STING increased ROS and DNA damage in iTreg and Th1 cells, and activating STING at 39 °C revealed that heat potentiates STING-induced inflammation in iTregs and Th1s, but Th1s experienced significantly more cell death in response to cGAMP and/or heat. Our data show that Th1 cells have increased expression of cGAS/STING at 39 °C, and at baseline (37 °C) compared to iTreg cells, indicating a potential mechanism for the resilience of iTreg cells during cell stress responses to heat and STING activation. Conclusion These data suggest a novel axis linking heat to STING that can be leveraged to understand and modulate Treg function in inflammation and promote CD4+ T cell responses without inducing significant cell death. These findings motivate further investigation into the mechanisms intertwining STING and heat in Tregs and suggest potential synergy between temperature and Treg-targeted STING modulators for broad applications in immunotherapies. Funding Source NIAID (F31AI186436) Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

Abstract Introduction Adoptive cell therapy (ACT) has demonstrated efficacy in hematologic malignancies but remains limited in solid tumors due to an immunosuppressive tumor microenvironment (TME) that restricts T cell infiltration, activation, and persistence. Activation of the stimulator of interferon genes (STING) pathway can reprogram the TME toward inflammation; however, systemic STING agonist delivery is hindered by poor tumor accumulation and dose-limiting toxicity. We hypothesized that targeted systemic delivery of a STING agonist using an albumin-hitchhiking nanobody platform could safely enhance ACT efficacy in solid tumors by reversing the immunosuppressive TME. Methods We developed albumin-hitchhiking nanobody—STING agonists (AHNSA) and evaluated them as an adjuvant to ACT in a TCR-transgenic OTI T cell transfer model using MC38-OVA tumors. Dosing and timing of AHNSA relative to ACT were optimized. Tumor-infiltrating immune cells and transferred T cells were analyzed by flow cytometry and IHC to assess activation, proliferation, exhaustion, and cytotoxic potential, as well as global changes in TME composition. Results Systemic AHNSA administration following OTI T cell transfer significantly improved survival compared to ACT alone. AHNSA treatment increased infiltration of both innate immune cells and adoptively transferred T cells into tumors. Transferred T cells displayed enhanced activation and proliferation with reduced expression of exhaustion markers. Bulk tumor immune profiling revealed enrichment of pro-inflammatory populations, including M1 macrophages, dendritic cells, and CD8+ T cells, alongside depletion of immunosuppressive subsets such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. These findings indicate effective reversal of TME immunosuppression. Ongoing studies are extending this approach to a fully immunocompetent CAR-T model. Conclusion AHNSA represents a promising strategy to overcome TME-mediated resistance and enhance ACT efficacy in solid tumors. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer’s disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS.

The enhancement of antitumour immunity via agonists of the stimulator of interferon genes (STING) pathway is limited by pharmacological barriers. Here we show that the covalent conjugation of a STING agonist to anti-albumin nanobodies via site-selective bioconjugation chemistries prolongs the circulation of the agonist in the blood and increases its accumulation in tumour tissue, stimulating innate immune programmes that increased the infiltration of activated natural killer cells and T cells, which potently inhibited the growth of mouse tumours. The technology is modular, as demonstrated by the recombinant integration of a second nanobody domain targeting programmed death-ligand 1 (PD-L1), which further increased the accumulation of the agonist in tumours while blocking immunosuppressive PD-1/PD-L1 interactions. The bivalent nanobody–STING agonist conjugate stimulated robust antigen-specific T-cell responses and long-lasting immunological memory and conferred enhanced therapeutic efficacy. It was also effective as a neoadjuvant treatment to adoptive T-cell therapy. As a modular approach, hitchhiking STING agonists on serum albumin may serve as a broadly applicable strategy for augmenting the potency of systemically administered cancer immunotherapies. A modular anti-albumin nanobody conjugated to a STING agonist enhances antitumour immunity by improving pharmacokinetics, tumour accumulation and immune responses, inhibiting murine tumour growth and enhancing cancer immunotherapies.

Intratumoral immunotherapy is a promising strategy for stimulating local and systemic antitumor immunity while eliminating or reducing immune-related adverse events often attendant to systemic administration. Activation of the cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) at tumor sites stimulates innate immunity that can potentiate a T cell-dependent adaptive antitumor immune response. However, the activity and efficacy of 5'-triphosphate RNA (3pRNA) agonists of RIG-I are hindered by poor in vivo stability, rapid degradation, limited cellular uptake, and inefficient cytosolic delivery. To overcome these challenges, we developed RIG-I-activating nanoparticles (RANs) assembled using a flash nanoprecipitation (FNP) process to load a potent stem-loop 3pRNA (SLR) RIG-I agonist into endosome-destabilizing polymeric nanoparticles. We leveraged FNP to induce turbulent micromixing among a corona-forming poly(ethylene glycol)-block-(dimethylaminoethyl methacrylate-co-butyl methacrylate) (PEG-DB) diblock copolymer, a hydrophobic core-forming DB counterpart, and an SLR RIG-I agonist, resulting in the self-assembly of densely loaded nanoparticles that promoted endosomal escape and cytosolic delivery of 3pRNA cargo. Through optimization of polymer properties and inlet feed ratios, we developed RANs with high and improved loading efficiency and increased serum stability relative to a previously reported micelleplex formulation assembled via electrostatic complexation with PEG-DB polymers. We found that optimized RANs exhibited potent immunostimulatory activity in vitro and in vivo when delivered intratumorally. As a result, in preclinical models of MC38 colon cancer and B16.F10 melanoma, intratumoral administration of RANs suppressed tumor growth and increased survival time relative to vehicle controls. Collectively, this work demonstrates that FNP can be harnessed as a versatile and scalable process for the efficient loading of nucleic acids into polymeric nanoparticles and highlights the potential of RANs as a translationally promising platform for intralesional cancer immunotherapy.

Pharmacologic activation of the stimulator of interferon genes (STING) pathway has broad potential applications, including the treatment of cancer and viral infections, which has motivated the synthesis and testing of a diversity of STING agonists as next generation immunotherapeutics. A promising class of STING agonists are the non-nucleotide, small molecule, dimeric-amidobenzimidazoles (diABZI), which have been recently used in the synthesis of polymer- and antibody-drug conjugates to improve pharmacokinetics, modulate biodistribution, and to confer other favorable properties for specific disease applications. These approaches have leveraged diABZI variants functionalized with reactive handles and enzyme-cleavable linkers at the 7-position of the benzimidazole for conjugation to and tunable drug release from carriers. However, since this position does not interact with STING and is exposed from the binding pocket when bound in an "open lid" configuration, we sought to evaluate the activity of macromolecular diABZI conjugates that lack enzymatic release and are instead conjugated to polymers via a stable linker. By covalently ligating diABZI to 5 or 20 kDa mPEG chains via an amide bond, we surprisingly found that these conjugates could activate STING in vitro. To further evaluate this phenomenon, we designed a diABZI-functionalized RAFT chain transfer agent that provided an enabling tool for synthesis of large, hydrophilic, dimethylacrylamide (DMA) polymers directly from a single agonist and we found that these conjugates also elicited STING activation in vitro with similar kinetics to highly potent small molecule analogs. We further demonstrated the in vivo activity of these macromolecular diABZI platforms, which inhibited tumor growth to a similar extent as small molecule variants. Using flow cytometry and fluorescence microscopy to evaluate intracellular uptake and distribution of Cy5-labeled analogs, our data indicate that although diABZI-DMA conjugates enter cells via endocytosis, they can still colocalize with the ER, suggesting that intracellular trafficking processes can promote delivery of endocytosed macromolecular diABZI compounds to STING. In conclusion, we have described new chemical strategies for the synthesis of stable macromolecular diABZI conjugates with unexpectedly high immunostimulatory potency, findings with potential implications for the design of polymer-drug conjugates for STING agonist delivery that also further motivate investigation of endosomal and intracellular trafficking as an alternative route for achieving STING activation.

A promising class of stimulator of interferon genes (STING) agonists is the non-nucleotide, small molecule, dimeric amidobenzimidazoles (diABZI), which have recently been incorporated into polymer- and antibody-drug conjugates to improve pharmacokinetics and modulate biodistribution for disease-specific applications. These approaches have leveraged diABZI variants functionalized at the 7-position of the benzimidazole for conjugation and tunable drug release from carriers. However, since this position does not interact with STING and is exposed from the binding pocket when bound in an "open lid" configuration, we sought to evaluate the activity of macromolecular diABZI conjugates that lack stimuli-responsive release and are instead conjugated to polymers via a stable amide linker. By synthesizing stable mPEG-diABZI conjugates and N,N-dimethylacrylamide (DMA) homopolymers from a diABZI-functionalized reversible addition-fragmentation chain-transfer (RAFT) agent, we found that these conjugates could activate STING in vitro with similar kinetics to highly potent diABZI analogues. Our data indicate that although diABZI-DMA conjugates enter cells via endocytosis, they can still colocalize with the ER, suggesting that intracellular trafficking processes can promote the delivery of endocytosed macromolecular diABZI compounds to STING. Furthermore, we demonstrated the in vivo activity of these macromolecular diABZI platforms, which inhibited tumor growth to a similar extent as small molecule variants. In conclusion, we have described new chemical strategies for the synthesis of stable macromolecular diABZI conjugates with unexpected immunostimulatory activity─findings that have potential implications for the design of polymer-diABZI conjugates and further motivate investigation of endosomal and intracellular trafficking as an alternative route for STING activation.

Vaccine adjuvants stimulate innate immunity to enhance and shape adaptive immune responses. However, approved adjuvants typically elicit weak CD8+ T cell responses to protein- and peptide-based vaccines, motivating an investigation into the discovery and testing of new adjuvants. Unedited forms of endogenous Alu RNAs are sensed by pattern recognition receptors (PRRs) to trigger sterile inflammation, and therefore we hypothesized that synthetic Alu RNA molecules could be harnessed as vaccine adjuvants. To enhance their intracellular delivery, Alu RNA was copackaged with a model antigen into polymer nanoparticles that promoted endosomal escape of Alu RNA to the cytosol. Using this nanovaccine formulation, we found that Alu RNA activated antigen-presenting cells in vitro and in vaccine-site draining lymph nodes in vivo. Furthermore, we demonstrated that vaccine formulations containing Alu RNA as an adjuvant elicited comparable CD8+ T cell responses to those containing the common but highly heterogeneous RNA adjuvant PolyIC, and that this response protected mice from tumor challenge. Based on this, we further evaluated the antitumor efficacy of nanovaccine formulations containing Alu RNA adjuvants in mice with established tumors, again observing comparable responses to formulations containing PolyIC. Finally, we found that nanovaccines adjuvanted with Alu RNA could improve responses to anti-PD-1 immune checkpoint blockade in tumor-bearing mice. Overall, this study demonstrates that unedited Alu RNA coformulated with antigen in polymer nanoparticles can be harnessed as an effective vaccine adjuvant for stimulating CD8+ T cell responses with antitumor function and may offer a sequence-defined alternative to PolyIC.

B7-H4 expression does not correlate with resistance to chemotherapy + immunotherapy in human breast tumors. Patients were from the I-SPY2 clinical trial (paclitaxel control and pembrolizumab arms) or the TBCRC 043 clinical trial (carboplatin control and atezolizumab arms). A, In breast tumors from the I-SPY2 clinical trial (control and pembrolizumab arms), B7-H4 expression is higher in TNBC tumors compared with HR+ tumors. Data were analyzed by unpaired t test. B, In the same patient cohort, B7-H4 expression is not higher in grade III tumors compared with grade I (orange dots) or II. Data analyzed by unpaired t test. C and D, B7-H4 expression is not correlated with pCR in tumors regardless of HR status, treated with either paclitaxel or paclitaxel + pembrolizumab (ICI). Data analyzed by unpaired t test. E, EFS in HR+ (n = 89) and TNBC (n = 62) tumors from the I-SPY2 cohort. Tumors with high B7-H4+ expression (top 33% of patients) have worse EFS when treated with paclitaxel alone and no survival benefit when treated with paclitaxel + ICI. Data were analyzed by log-rank Mantel–Cox test. F, In the metastatic setting, PFS stratified by B7-H4 expression (top and bottom 33% of cohort) from primary breast biopsy or metastatic lesion in patients from the TBCRC 043 trial does not correlate with B7-H4 expression in either control or carboplatin + atezolizumab (ICI) groups. Data were analyzed by log-rank Mantel–Cox test. G and H, We also assessed survival by treatment status. Metastatic tumors (H) from TBCRC 043 with high B7-H4 expression had significantly improved PFS to ICI, and nonmetastatic tumors (I-SPY2) had minimal improvement to ICI (G). Data were analyzed by log-rank Mantel–Cox test. n = 151 patients for A–E and G; n = 91 patients for F and H.

Mammalian cells release a heterogeneous array of extracellular vesicles (EVs) that contribute to intercellular communication by means of the cargo that they carry. To resolve EV heterogeneity and determine if cargo is partitioned into select EV populations, we developed a method named "EV Fingerprinting" that discerns distinct vesicle populations using dimensional reduction of multiparametric data collected by quantitative single-EV flow cytometry. EV populations were found to be discernible by a combination of membrane order and EV size, both of which were obtained through multiparametric analysis of fluorescent features from the lipophilic dye Di-8-ANEPPS incorporated into the lipid bilayer. Molecular perturbation of EV secretion and biogenesis through respective ablation of the small GTPase Rab27a and overexpression of the EV-associated tetraspanin CD63 revealed distinct and selective alterations in EV populations, as well as cargo distribution. While Rab27a disproportionately affects all small EV populations with high membrane order, the overexpression of CD63 selectively increased the production of one small EV population of intermediate membrane order. Multiplexing experiments subsequently revealed that EV cargos have a distinct, nonrandom distribution with CD63 and CD81 selectively partitioning into smaller vs larger EVs, respectively. These studies not only present a method to probe EV biogenesis but also reveal how the selective partitioning of cargo contributes to EV heterogeneity.

Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T H 1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T H 1 cells subjected to such temperatures died, surviving T H 1 cells exhibited increased mitochondrial mass and enhanced activity. Electron transport chain complex 1 (ETC1) was rapidly impaired under fever-range temperatures, a phenomenon that was specifically detrimental to T H 1 cells. T H 1 cells with elevated DNA damage and ETC1 signatures were also detected in human chronic inflammation. Thus, fever-relevant temperatures disrupt ETC1 to selectively drive apoptosis or adaptation of T H 1 cells to maintain genomic integrity and enhance effector functions.

Supplemental Figure 1. MMTV-neu epithelial and mesenchymal cells did not undergo EMT or MET. Single cell-derived clones were isolated from parental, heterogeneous MMTV-neu cells by FACS single-cell limiting dilutions. 16 epithelial and 10 mesenchymal single-cell clones were passaged independently for over 20 passages. After 13 passages, conditioned media from the alternate cell line was collected, filtered, and applied to a passage of each single-cell clone. Independent clones or clones treated with conditioned media did not undergo epithelial-to-mesenchymal or mesenchymal-to-epithelial transition in vitro. Two representative clones from each cell line are shown above.

Despite success in treating hematologic malignancies, chimeric antigen receptor-T cell (CAR-T) therapy still faces multiple challenges that have halted progress, especially against solid tumors. Recent advances in nanoscale engineeirng provide several avenues for overcoming these challenges, including more efficienct programming of CAR-Ts ex vivo, promoting immune responsiveness in the tumor microenvironment (TME) in vivo, and boosting CAR-T function in situ. Here, we summarize recent innovations that leverage nanotechnology to directly address the major obstacles that impede CAR-T therapy from reaching its full potential across various cancer types. We conclude with a commentary on the state of the field and how nanotechnology can shape the future of CAR-T and adoptive cell therapy in immuno-oncology.

Supplemental Figure 2. B7-H4 expression is not affected by type I or II interferon or TGF-β treatment in vitro. MMTV-neu epithelial cells that have high levels of endogenous B7-H4 were treated for 72 hours with IFNα or IFNγ at 100ng/mL. B7-H4 expression was analyzed by flow cytometry (n=4-5 per group). Similarly, B7-H4 expression was not altered by TGF-β expression (10 ng/mL) in vitro after 72 hours. Data were analyzed by One-way ANOVA or unpaired t-test.

A genetically engineered variant of the stimulator of interferon genes (STING) protein is delivered to cancer cells, showing potential for clinical impact.

Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment and led to complete and durable responses, but only for a minority of patients. Resistance to ICB can largely be attributed to insufficient number and/or function of antitumor CD8(+) T cells in the tumor microenvironment. Neoantigen targeted cancer vaccines can activate and expand the antitumor T cell repertoire, but historically, clinical responses have been poor because immunity against peptide antigens is typically weak, resulting in insufficient activation of CD8(+) cytotoxic T cells. Herein, we describe a nanoparticle vaccine platform that can overcome these barriers in several ways. First, the vaccine can be reproducibly formulated using a scalable confined impingement jet mixing method to coload a variety of physicochemically diverse peptide antigens and multiple vaccine adjuvants into pH-responsive, vesicular nanoparticles that are monodisperse and less than 100 nm in diameter. Using this approach, we encapsulated synergistically acting adjuvants, cGAMP and monophosphoryl lipid A (MPLA), into the nanocarrier to induce a robust and tailored innate immune response that increased peptide antigen immunogenicity. We found that incorporating both adjuvants into the nanovaccine synergistically enhanced expression of dendritic cell costimulatory markers, pro-inflammatory cytokine secretion, and peptide antigen cross-presentation. Additionally, the nanoparticle delivery increased lymph node accumulation and uptake of peptide antigen by dendritic cells in the draining lymph node. Consequently, nanoparticle codelivery of peptide antigen, cGAMP, and MPLA enhanced the antigen-specific CD8(+) T cell response and delayed tumor growth in several mouse models. Finally, the nanoparticle platform improved the efficacy of ICB immunotherapy in a murine colon carcinoma model. This work establishes a versatile nanoparticle vaccine platform for codelivery of peptide neoantigens and synergistic adjuvants to enhance responses to cancer vaccines.

Supplementary Table 1. DE genes between isotype treated and anti-PD-L1 treated EMT6 tumors.