The benefits of the combination cytostatic drug regimen was not mediated by the T cells and B immune cells involved in adaptive immunity, but by the innate immune system’s NK cells.1


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That finding suggests that lung cancer that has evaded antitumor immune attack can be resensitized using cytostatic chemotherapy, and bolsters the case that chemotherapy can improve immunotherapy’s efficacy — as well as work on anticancer immunotherapies that go beyond agents designed to unleash adaptive antitumor immunity, like immune checkpoint blockade.1,2

NK cells can detect and kill senescent tumor cells, and cytostatic drug regimens might, therefore, prove to work synergistically with existing immune checkpoint inhibitor immunotherapies.1

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The findings also suggest new paths forward in managing cancers with supposedly “undruggable” gene mutations like KRAS. The researchers plan next to study the combination of cytostatic and immunotherapy regimens.1,2

“However, several hurdles remain on the road to therapy-induced senescence as a means of treating cancer: optimization of the dose schedules and combinations required to induce cellular senescence and antitumor immunity, while overcoming the protumorigenic properties of senescent cells and the SASP [the RB protein-activated, senescence-associated secretory phenotype],” cautioned Stéphanie Cornen, PharmD, PhD, and Eric Vivier, PhD, of Innate Pharma in Marseille, France, in a companion essay published alongside the study in Science.2 “SASP has been described as a double-edged sword because it can also induce tumor-promoting effects such as angiogenesis, epithelial-to-mesenchymal transition, and metastasis. It thus remains unclear whether it is preferable to induce senescence rather than cell death.”

References

  1. Ruscetti M, Leibold J, Bott MJ, et al. NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination. Science. 2018;362(6421):1416-1422.
  2. Cornen S, Vivier E. Chemotherapy and tumor immunity: Inducing senescence in tumor cells stimulates antitumor innate immune responses. Science. 2018;362(6421):1355-1356.
  3. Tontonoz, M. Drugs that stall—but don’t kill—cancer cells are an untapped resource, study suggests [press release]. https://www.mskcc.org/blog/drugs-stall-don-t-kill-cancer-cells-are-untapped-resource-study-suggests?_subsite=research-ski. Published December 20, 2018. Accessed January 14, 2018.