Analysis of the cellular immune response to and adoptive immunotherapy of a BALB/c lymphoma that cross-reacts with normal DBA/2 cells

Sensi, Marialuisa; Grazioli, Laura; Parmiani, Giorgio

doi:10.1007/bf00199362

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Followup studies employed almost the identical experimental protocol, but with the tumor implantation done before conditioning. As YC8-specific resistance seemed to be attributed to immunization of the BALB/c mice with DBA/2 splenocytes (361,412), administration of these cells (alloantigen) was paired as US together with the presentation of camphor odor as CS. The results displayed a conditioned resistance to YC8 lymphoma in female mice (177).…”

Section: Tumorsmentioning

confidence: 99%

Pavlovian Conditioning of Immunological and Neuroendocrine Functions

Hadamitzky

Lückemann

Pacheco-López

et al. 2020

Physiological Reviews

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The phenomenon of behaviorally conditioned immunological and neuroendocrine responses has been investigated for the past 100 years. The observation that peripheral immune functions can be modified by associative learning processes was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. This phenomenon was re-discovered 45 years ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be suppressed or activated via distinct associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provides fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.

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Section: Tumorsmentioning

confidence: 99%

Pavlovian Conditioning of Immunological and Neuroendocrine Functions

Hadamitzky

Lückemann

Pacheco-López

et al. 2020

Physiological Reviews

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“…The i.v, administration of specific tumor-immune T lymphocytes can cure most mice bearing 3-day established YC8 tumors (Colombo et al, 1984;Sensi et al, 1986). Here we show that the curative activity of immune effector cells is pro~re~sively lost when the~nset of !reatment is delayed, indicating that tumor burden IS most likely a crucial factor which limits the efficacy of this therapy.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of adoptive immunotherapy by cis‐diamminedichloroplatinum(II), but not by doxorubicin, on a disseminated mouse lymphoma and its association with reduction of tumor burden

Formelli

Rossi

Sensi

et al. 1988

Intl Journal of Cancer

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The therapeutic effect of a combination therapy employing syngeneic anti-tumor immune T lymphocytes and either doxorubicin (DX) or cis-diamminedichloroplatinum II (DDP) was tested on BALB/c mice bearing a disseminated, weakly immunogenic lymphoma (YC8) which metastasizes mainly to the liver. Therapy with specific tumor-immune lymphocytes alone cure 80-100% mice bearing 3-day established tumors. The same effector cells, however, were less effective in mice at a more advanced stage of the disease (day 5) and ineffective when treatment was further delayed (day 7). Chemotherapeutic treatment alone with DX or DDP given i.p. at the maximal tolerated doses was less effective than immune lymphocytes on 3-day tumors since cures were very seldom observed, but both drugs prolonged survival time even when administered on day 7. While DX did not enhance the antitumor effect of immune lymphocytes on 5-day tumors, the association of DDP with immunotherapy by giving the 2 modalities sequentially according to the two sequences (i.e., chemotherapy before immunotherapy and vice versa) with a 2-day interval, was significantly more effective than each treatment alone. Like mice cured by immunotherapy alone, most of the animals cured by chemo-immunotherapy developed a systemic transplantation immunity to the tumor as revealed by the specific rejection of a second lethal tumor challenge 90 days after the first tumor inoculum. The higher activity of DDP compared with DX in potentiating the effect of immunotherapy was shown to be associated with a greater reduction of tumor burden in the liver, whereas the 2 drugs gave a similar reduction of tumor burden in other organs, as determined from bioassay of tumor-bearing organs of chemotherapy-treated mice. These results indicate that combination of chemotherapy with immunotherapy may improve the effects of each treatment alone, and that the synergistic effect is associated with the reduction of the tumor load in the main organ (liver) of tumor dissemination.

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“…The susceptibility of this tumor to other chemotherapeutic agents, as well as to immune effectors, has been extensively investigated in previous works (Colombo et d . , 1984;Formelli et al, 1988;Sensi et al, 1986). It was found that other anti-tumor drugs such as doxorubicin (DX) or cisplatinum (DDP) were not curative (Formelli et al, 1988).…”

Section: Bcnu Balb/c Anti-yca Donorsmentioning

confidence: 99%

“…It was found that other anti-tumor drugs such as doxorubicin (DX) or cisplatinum (DDP) were not curative (Formelli et al, 1988). Immune lymphocytes could be highly effective, but only when administered to mice bearing a small tumor (3-day tumor burden) (Colombo et al, 1984;Sensi et al, 1986). The effect of DDP, but not of DX, however, could be greatly improved by the addition of immune effectors resulting in the cure of mice bearing a 5-day tumor burden (Formelli et al, 1988).…”

Section: Bcnu Balb/c Anti-yca Donorsmentioning

confidence: 99%

Eradication of a disseminated mouse lymphoma by 1,3‐BIS(2‐chloroethyl)‐1‐nitrosourea is immunologically mediated and accompanied by de novo generation of anti‐tumor cytotoxicity

Sensi

Bergomi

Formelli

et al. 1990

Intl Journal of Cancer

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The anti-tumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YC8). A single i.p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i.v. inoculum of 10(4) YC8 cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5-day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU-cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti-tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2-week period elapsed after BCNU injection before an anti-tumor cytotoxic T-lymphocyte (CTL) response could be generated by spleen cells of BCNU-treated 5-day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine-activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU-treated 5-day TB and BCNU-treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14, concomitantly with the generation of anti-tumor cytotoxicity by 5-day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU 1 week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin-2.

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Analysis of the cellular immune response to and adoptive immunotherapy of a BALB/c lymphoma that cross-reacts with normal DBA/2 cells

Cited by 6 publications

References 26 publications

Pavlovian Conditioning of Immunological and Neuroendocrine Functions

Pavlovian Conditioning of Immunological and Neuroendocrine Functions

Potentiation of adoptive immunotherapy by cis‐diamminedichloroplatinum(II), but not by doxorubicin, on a disseminated mouse lymphoma and its association with reduction of tumor burden

Eradication of a disseminated mouse lymphoma by 1,3‐BIS(2‐chloroethyl)‐1‐nitrosourea is immunologically mediated and accompanied by de novo generation of anti‐tumor cytotoxicity

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