Specific cellular immune response elicited by the necrotic tumor cell-stimulated macrophages

Yuan, Xiaolin; Li, Weina; Cui, Yifen; Zhan, Qing-Guang; Zhang, Chunlei; Yang, Zhen; Li, Xiaohuan; Li, Shengfan; Guan, Qing‐Lin; Sun, Xiuyan

doi:10.1016/j.intimp.2015.04.056

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…However, when cryoablation is to be used as an in vivo vaccination tool, the variation in the mechanistic processes of fast and slow freeze rates on cell injury may influence the balance of necrosis/apoptosis, and the quality of the immune responses (11,12,15). There are reports indicating that tumor necrosis elicits immunogenic responses (16,17), whereas some contradicting studies suggest that apoptosis (as opposed to necrosis) is a strong driver of anti-tumor immune responses (18,19). A previous study by Sabel et al reported the advantage of fast freeze over slow freeze, but information regarding necrosis/apoptosis in the ablated tissue, and an in-depth characterization of immune responses appear lacking (11).…”

Section: Discussionmentioning

confidence: 99%

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma

et al. 2021

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The emergence of ablative therapies has revolutionized the treatment of inoperable solid tumors. Cryoablation stands out for its uniqueness of operation based on hypothermia, and for its ability to unleash the native tumor antigens, resulting in the generation of anti-tumor immune responses. It is not clearly understood how alterations in the rate of freeze impact the immune response outcomes. In this study, we tested fast freeze and slow freeze rates for their locoregional effectiveness and their ability to elicit immune responses in a B16F10 mouse model of melanoma. Tumor bearing mice treated with fast freeze protocol survived better than the ones treated with slow freeze protocol. Fast freeze resulted in a higher magnitude of CD4+ and CD8+ T-cell responses, and a significantly extended survival post re-challenge. Thus, fast freeze rate should be applied in any future studies employing cryoablation as an in vivo vaccination tool in conjunction with targeted immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma

et al. 2021

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“…Although cancer cell vaccines have been studied as a promising cancer treatment strategy for decades, the antigen form, which is the most effective in cancer vaccine preparation, has not yet been clearly demonstrated. The antitumor efficiency of vaccines prepared by tumor cell lysate and glutaraldehyde-fixed tumor cells, two commonly used antigen forms ( 21 – 23 ), was evaluated in the present study. The results of the present study demonstrated that the tumor cell lysate-based vaccine induced increased significant inhibition on tumor growth and metastasis compared with the glutaraldehyde-fixed tumor cell-based vaccine, which may be the result of the more evident antigen-specific humoral and cellular immune responses.…”

Section: Discussionmentioning

confidence: 99%

Inï¿½vivo antitumor activity evaluation of cancer vaccines prepared by various antigen forms in a murine hepatocellular carcinoma model

et al. 2017

Oncol Lett

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Cancer cell vaccines with strong specificity and low tolerance have been revealed to be a promising option for oncology treatment. Various antigen forms, including tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively used in cancer vaccine preparation. However, the most effective antigen form has not yet been identified. In the present study, the antitumor efficiency of vaccines prepared by these two antigen forms was systematically investigated. Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22 hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL were administrated by subcutaneous immunization in prophylactic and therapeutic strategies. The results of the present study revealed that H22-TCL immunization induced more significant inhibition on tumor growth and metastasis compared with Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated that H22-TCL vaccine induced larger areas of continuous necrosis within tumors compared to the Fixed-H22-CELL vaccine, which was associated with the extent of tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more evident antigen-specific antibody responses compared with the Fixed-H22-CELL injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more significant T lymphocytes proliferation compared with that from Fixed-H22-CELL-treated mice. All the results indicated that whole tumor cell lysate may be a more effective antigen form in cancer vaccine preparation compared with glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific humoral and cellular immune responses resulted with a superior antitumor efficiency. This would have important clinical signification for cancer vaccine preparation and serve a role in prompting this to other researchers.

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“…Activation of immunocytes has a key role in antitumor immunotherapy. Numerous studies have reported that TCL can activate immunocytes (22)(23)(24); however, it remains unclear as to what components present in TCL possess this ability. TCL is a protein mixture produced by lysed tumor cells; the majority of these proteins are involved in signaling pathways associated with cell division and activation.…”

Section: Discussionmentioning

confidence: 99%

Detection of RACK1 and CTNNBL1-induced activation of mouse splenocytes using an immunoprecipitation-based technique

Dong

Dai

et al. 2017

Molecular Medicine Reports

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Tumor cell lysates (TCLs) have been reported to induce antitumor immunity; however, it remains unclear which elements serve a role in this process. The present study identified 768 proteins that were upregulated in TCL prepared from Lewis lung cancer cells compared with the lysate from type II alveolar epithelial cells. Among the proteins that were upregulated in TCL, receptor for activated C kinase 1 (RACK1) and catenin β‑like 1 (CTNNBL1) are closely associated with cell proliferation and the inhibition of apoptosis. To determine the role of these proteins in TCL, a protein extraction method was designed, which was based on immunoprecipitation. Using this method, RACK1 and CTNNBL1 were extracted, whereas the other proteins within the TCL were not affected. The modified TCL exhibited a stronger ability to induce splenocyte apoptosis, whereas the ability to promote cell activation was reduced. These findings suggested that the TCL depends on RACK1 and CTNNBL1 to activate mouse immunocytes, including monocytes and B lymphocytes, and inhibit apoptosis. Therefore, the present study may provide information regarding the composition of TCLs and their positive regulatory effect on immunocytes.

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Specific cellular immune response elicited by the necrotic tumor cell-stimulated macrophages

Cited by 7 publications

References 29 publications

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma

Inï¿½vivo antitumor activity evaluation of cancer vaccines prepared by various antigen forms in a murine hepatocellular carcinoma model

Detection of RACK1 and CTNNBL1-induced activation of mouse splenocytes using an immunoprecipitation-based technique

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