Correction: Reschke, R.; Olson, D.J. Leveraging STING, Batf3 Dendritic Cells, CXCR3 Ligands, and Other Components Related to Innate Immunity to Induce a “Hot” Tumor Microenvironment That Is Responsive to Immunotherapy. Cancers 2022, 14, 2458

The authors would like to make the following corrections to their published paper [...].

4. Change the title of Section 3.1 from "Inducing Chemokines" to "Inducing Chemokines and Cytokines", and add the following content to the original text, starting from the end of the paragraph: …"A combination treatment consisting of chemotherapy (cisplatin), COX-2 inhibitor (celecoxib), type I IFN, and a TLR3 agonist (rintalomid) also led to successful induction of CXCL9-11 in patients with epithelial ovarian cancer [60].In the future, this approach will be combined with DC vaccination to achieve optimal tumor control of "cold" tumors via cytotoxic T cell recruitment.In mice, the administration of heterodimeric IL-15 resulted in increased levels of XCL1, IFNγ, and CD103+ DCs, as well as CXCL9/10 production, and the recruitment of NK and T cells [47].Another a ractive avenue would be to leverage radiation therapy to induce cytokine/chemokine production.Radiation therapy in melanoma-bearing mice induced Type I IFN and CXCL10 production by myeloid cells because cytosolic dsDNA released from dying cancer cells activates the STING pathway in dendritic cells [61].
All these approaches constitute important new treatment avenues for "cold" tumors.However, these strategies of chemokine and cytokine induction only work well when key innate immune cells such as Batf3 DCs are present in the TME.Another limiting factor is the right formulation and delivery of these components.Systemic application or an increased dosage of CXCL9-11, for example, may lead to unwanted immune-related adverse events.Severe adverse events can lead to the discontinuation of checkpoint blockade therapy.Innovative delivery strategies might help circumvent toxicity.In a mouse model, masking IL12 by fusing it to a domain of the IL12 receptor prevented systemic toxicity despite intravenous application [62].With this modification, the anti-tumor effect remained intact".5. Change the title of Section 3.1 from "Inducing Chemokines" to "Inducing Chemokines and Cytokines", and add the following content to the original text, starting from the end of the paragraph: . .."A combination treatment consisting of chemotherapy (cisplatin), COX-2 inhibitor (celecoxib), type I IFN, and a TLR3 agonist (rintalomid) also led to successful induction of CXCL9-11 in patients with epithelial ovarian cancer [60].In the future, this approach will be combined with DC vaccination to achieve optimal tumor control of "cold" tumors via cytotoxic T cell recruitment.In mice, the administration of heterodimeric IL-15 resulted in increased levels of XCL1, IFNγ, and CD103+ DCs, as well as CXCL9/10 production, and the recruitment of NK and T cells [47].Another attractive avenue would be to leverage radiation therapy to induce cytokine/chemokine production.Radiation therapy in melanomabearing mice induced Type I IFN and CXCL10 production by myeloid cells because cytosolic dsDNA released from dying cancer cells activates the STING pathway in dendritic cells [61].
All these approaches constitute important new treatment avenues for "cold" tumors.However, these strategies of chemokine and cytokine induction only work well when key innate immune cells such as Batf3 DCs are present in the TME.Another limiting factor is the right formulation and delivery of these components.Systemic application or an increased dosage of CXCL9-11, for example, may lead to unwanted immune-related adverse events.Severe adverse events can lead to the discontinuation of checkpoint blockade therapy.Innovative delivery strategies might help circumvent toxicity.In a mouse model, masking IL12 by fusing it to a domain of the IL12 receptor prevented systemic toxicity despite intravenous application [62].With this modification, the anti-tumor effect remained intact".
6. Revise the title of Section 3.2 from "Adverse Effects Caused by Chemokines" to "Adverse Effects Caused by Chemokines and Cytokines".Revise the first sentence of Section 3.2 from "Systemic upregulation of CXCL9/10/11 can contribute to inflammation and autoimmunity such as Alopecia areata, Vitiligo, autoimmune arthritis, type 1 diabetes, or adult-onset Still's disease" to "Systemic upregulation of CXCL9/10/11 can contribute to inflammation and autoimmunity such as Alopecia areata, Vitiligo, autoimmune arthritis, type 1 diabetes, or adult-onset Still's disease as well as immunotherapy-induced toxicity [62-66]".Add the sentence "Increased levels of CXCL9-11 in the blood during checkpoint blockade therapy were also associated with occurrence of irAE [68]" as the third sentence in Section 3.2.Add "Similarly, systemic administration of cytokines can lead to severe and lifethreatening toxicity.IL12, for example, results in an extensive production of systemic IFN-γ from NK cells [62].Accordingly, potential off-tumor effects of systemic administration of cytokines must always be considered in clinical trial designs of these therapies" as the last sentence in Section 3.2.
7. Revise Table 1 title and content to the following version (added lines TLR3, IL-12 (mouse) and IL-15 (mouse); removed lines TLR3+, Flt3L+, B7-H3+, 4-1BBL+, and IL-12 (human)).Add it's citation after the sentence "Two recent reports propose alternate administration routes for the more stable STING agonists named MSA-2 and SR-717 configured in a closed confirmation [28,29]" in Section 2. 8. Delete contents of the original Section 4 and Figure 4. 9. Add "Checkpoint blockade therapy is already used for many metastasized solid tumors but is also well accepted in the adjuvant setting for, e.g., melanoma patients [74]" as the last sentence in Section 4, "Conclusions".
10. Delete the original references 59-76, 81, and 82; add some new ones as references 42-49, 60, 61, 68 and 74; the original reference numbers starting from new reference 42 are also updated.The other references are also updated accordingly.The authors apologize for any inconvenience caused and state that the results and scientific conclusions are unaffected.This correction was peer reviewed by the previous referees and approved by the Academic Editor.The original publication has also been updated.

Figure 3 .
Figure 3. Chemokine/cytokine network in the tumor microenvironment.Tumor-derived CCL4 can a ract Batf3 DCs, and CXCL9/10 can recruit cytotoxic T cells to the tumor microenvironment.Natural Killer Cells a ract Batf3 DCs via XCL1 and CCL5.CCL4 can be administered with a fusion protein consisting of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor and XCL1 with a viral vector.APCs (in particular Batf3 DCs) can produce CXCL9/10/11, IL12, and IL15 and can recruit and activate NK and cytotoxic T cells.In turn, IFN-γ produced by CTLs can stimulate APCs.APCs are activated by STING or TLR agonists, which can contribute to CXCL9/10/11 production via IFNα/β.CXCL9/10/11 can be induced by oncolytic viruses or delivered with the help of virus-based vectors.

Figure 3 .
Figure 3. Chemokine/cytokine network in the tumor microenvironment.Tumor-derived CCL4 can attract Batf3 DCs, and CXCL9/10 can recruit cytotoxic T cells to the tumor microenvironment.Natural Killer Cells attract Batf3 DCs via XCL1 and CCL5.CCL4 can be administered with a fusion protein consisting of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor and XCL1 with a viral vector.APCs (in particular Batf3 DCs) can produce CXCL9/10/11, IL12, and IL15 and can recruit and activate NK and cytotoxic T cells.In turn, IFN-γ produced by CTLs can stimulate APCs.APCs are activated by STING or TLR agonists, which can contribute to CXCL9/10/11 production via IFNα/β.CXCL9/10/11 can be induced by oncolytic viruses or delivered with the help of virus-based vectors.

Table 1 .
Induction and delivery of components related to the innate immune system that synergize with immunotherapy: summary of recent preclinical and clinical studies.