Markedly induced asialoGM1 + CD8 + T cell production and enhancement of antimetastatic activity by interferon β with folic or folinic acid

Abstract

Either folic or folinic acid enhanced the antimetastatic activity of recombinant murine interferon beta (rMulFN beta) toward highly metastatic colon carcinoma 26 (Co 26Lu). Folinic acid administered with rMuIFN beta markedly increased asialoGM1+CD4+ and asialoGM1+CD8+ T cell production in the peritoneal cavity but not in the thymus and spleen. Peritoneal cells expressed killing activity toward Co 26Lu cells in vitro. In athymic nude mice, the above combination produced many asialoGM1+CD4+ and few asialoGM1+CD8+ T cells in the peritoneal cavity, but did not decrease lung metastatic colonies. AsialoGM1+CD4+ T cells would thus appear to have no or only very weak killing activity toward these tumor cells. The antimetastatic activity of folinic acid with rMuIFN beta was significantly decreased with anti-asialoGM1 and anti-CD8 antibodies. Inactivated CD8+ and asialoGM1+ cells cease to have killing activity toward Co 26Lu cells as shown by Winn's assay. AsialoGM1+CD8+ cell production was markedly induced in the peritoneal cavity by treatment with rMuIFN beta and folinic acid. AsialoGM1+CD8+ T cells may be inhibiting lung metastasis of Co 26Lu. Folinic acid and interferon are used in combination therapy with 5-fluorouracil for biochemical modulation. Folinic acid with interferon, as adjuvant therapy, may promote the induction of CD8+ T cell production with consequent prevention of metastasis.

Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes In Vitro

“…In mice, treatment with high levels of folate (50 mg/kg) enhances the IFN-␤-induced production of extrathymic CD4 ϩ and CD8 ϩ cells, as well as the antimetastatic activity of CD8 ϩ cells (53). Folate deficiency could have the reciprocal effect on PHA-activated CD8 ϩ cells, although it does not likely involve an irreversible inhibition of PHA activation.…”

NK cells orchestrate splenic cDC1 migration to potentiate antiviral protective CD8+ T cell responses

“…XCR1 expression increases cDC1 infiltration in XCL1-expressing inflammatory tumors (Böttcher et al, 2018). XCR1 was also suggested to help cDC1 interpreting guiding cues provided by NK1.1 + or AsialoGM1 + cells (Böttcher et al, 2018), which include not only NK cells but also NK T cells and certain subsets of CD8 + and CD4 + T cells (Iigo et al, 1997;Trambley et al, 1999;Slifka et al, 2000;Yamanokuchi et al, 2005;Kosaka et al, 2007;Moore et al, 2008;Nour-Eldine et al, 2018). Although NK cells are a critical source of XCL1, the contribution of the XCL1/XCR1 axis in cDC1/NK cell interactions has not been rigorously determined.…”