The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

Riedlinger, Gregory; Adams, Jonathan M.; Stehle, John; Blanks, Michael J; Sanders, Anne M.; Hicks, Amy M.; Willingham, Mark C.; Cui, Zheng

doi:10.1186/1471-2407-10-179

Cited by 17 publications

(18 citation statements)

References 17 publications

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“…On the other hand, such experimental results cast a certain doubt to the robustness of the SR/CR mouse model as a general cancer resistance model. Taken together, we conclude that innate immune cells from SR/CR cancer resistant mice seem to be functionally different from those from nonresistant controls and [14], and the restricted cancer resistance mechanism of SR/CR mice in the present experimental context appeared to be dependent on interactions between S180 cells and SR/CR leukocytes. The data substantiate that growth and spread of cancer cells are dependent on a complex interplay between the cancer cells and the host organism.…”

Section: Discussionmentioning

confidence: 50%

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

et al. 2013

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Few experimental models are available for the study of natural resistance to cancer. One of them is the SR/CR (spontaneous regression/complete resistance) mouse model in which natural resistance to a variety of cancer types appeared to be inherited in SR/CR strains of BALB/c and C57BL/6 mice. The genetic, cellular, and molecular effector mechanisms in this model are largely unknown, but cells from the innate immune system may play a significant role. In contrast to previous observations, the cancer resistance was limited to S180 sarcoma cancer cells. We were unable to confirm previous observations of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding recipient mice, the cancer disappeared gradually following infiltration of a large number of polymorphonuclear granulocytes and remarkably few lymphocytes in the remaining tumor tissues. This study confirmed that the in vivo growth and spread of cancer cells depend on a complex interplay between the cancer cells and the host organism. Here, hereditary components of the immune system, most likely the innate part, played a crucial role in this interplay and lead to resistance to a single experimental cancer type. The fact that leukocytes depleted of both CD4+/CD8+ and B cells from the cancer resistant donor mice could be transferred to inhibit S180 cancer cell growth in susceptible recipient mice support the vision of an efficient and adverse event free immunotherapy in future selected cancer types.

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Section: Discussionmentioning

confidence: 50%

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

et al. 2013

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“…57 One study has shown that increased direct contact between tumor cells and PMN plus macrophages in mice is responsible for resisting lethal doses of cancer cells. 70, 71 However, the molecular mechanism for such efficacy remains unclear.…”

Section: Direct Cancer and Innate Immune System Interactionsmentioning

confidence: 99%

Cancer and Innate Immune System Interactions

Liu

Zeng²

2012

Journal of Immunotherapy

147

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Passive immunotherapy, including adoptive T cell therapy and antibody therapy, has shown encouraging results in cancer treatment lately. However, active immunotherapy of solid cancers remains an elusive goal. It is now known that the human innate immune system recognizes pathogen-associated molecular patterns (PAMP) conserved among microbes or damage-associated molecular patterns (DAMP) released from tissue injuries to initiate adaptive immune responses during infection and tissue inflammation, respectively. In contrast, how the innate immune system recognizes endogenously arising cancer remains poorly understood at the molecular level, which poses a significant roadblock to the development of active cancer immunotherapy. We hereby review the current knowledge of how solid cancers directly and indirectly interact with cells of the human innate immune system, with a focus on the potential impact of such interactions to the resultant adaptive immune responses against cancer. We believe that understanding cancer and innate immune system interactions may allow us to better manipulate the adaptive immune system at the molecular level in order to develop effective active immunotherapy against cancer. Current and future perspectives in clinical development that exploits these molecular interactions are discussed.

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“…Studies on a mouse colony that show spontaneous regression of tumors and cancer resistance reveal that tumor regression requires both the infiltration of tumors with leukocytes, particularly PMNs, and the recognition of some undetermined surface markers on tumor cells [97]. …”

Section: Targeting Tumor-host Interactionmentioning

confidence: 99%

Novel Antibody-Based Proteins for Cancer Immunotherapy

Fuenmayor

Montano

2011

Cancers

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The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

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The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

Cited by 17 publications

References 17 publications

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

Cancer and Innate Immune System Interactions

Novel Antibody-Based Proteins for Cancer Immunotherapy

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