Moderne terapie nel trattamento del mesotelioma pleurico
Rossana Berardi
Clinica di Oncologia Medica Università Politecnica delle Marche
Ospedali Riuniti di Ancona
Incidenza dei tumori in Italia
Sopravvivenza a 5 anni in Italia
Amianto (IARC)
“Raro” tumore della pleura
Maschi:femmine = 3:1
Periodo di latenza: 20-40 anni dall’esposizione ambientale
Età: sesta-ottava decade
Agente patogenetico: asbesto (70-80% dei casi)
Tsao AS, et al. J Clin Oncol. 2009;27:2081-2090.
Mesotelioma: epidemiologia
Esposizione all’asbesto e rischio
individuale
Mutazione
BAP1?
Strategia terapeutica multimodale
Mutazione
BAP1? Radioterapia
chemioterapia
Chemioterapia
Mutazione
BAP1?
Limitata risposta obiettiva (<20%)
Migliori risultati con terapie di combinazione a più farmaci (cisplatino, pemetrexed)
Nuovi farmaci?
Ieri:
…tanti pazienti, una sola terapia…
Oggi:
… a ciascuno la sua
terapia!
BOMBE INTELLIGENTI
TERAPIE MIRATE
TERAPIE A BERSAGLIO
• Azione selettiva
• Minore tossicita’ sistemica
• Elevate risposte in subset
selezionati di pazienti
• Somministrazione orale
(piccole molecole, non anticorpi monoclonali)
TERAPIE A BERSAGLIO BIOMOLECOLARE
Entra in scena l’IMMUNOTERAPIA
nuova
…se il sistema immunitario è tanto potente,
perchè le persone sviluppano il cancro?
Cancers look like “self”
– Cancers are shaped by the host microenvironment
Is there a way to effectively and safely break tolerance to “self”?
Tumors actively defeat the host immune response
Cancer immunotherapy
Shankaran V, et al. Nature. 2001;410:1107-1111.
In other words, competent immune systems force the tumors to figure
out how to survive in hostile environments
Immunocompetent Mice Reject Tumors Originating in Immunodeficient Mice
“Antigen-specific”
Specific priming of immune system
antigen-specific antibodies & cytotoxic T cells
“Non antigen-specific”
Enhancement of innate/adaptive immune system
altered action of e.g. dendritic cells.
Cancer immunotherapy
Cancer immunotherapy: any interaction
with the immune system to treat cancer
Cancer-vaccination therapy
Immunomodulation therapy
Res
po
nse
Time (months) 0 6 12
IMMUNOTHERAPY
Chemotherapy and Targeted Therapies
Chemotherapy/Targeted Agents and
Immunotherapy Differ in Action and Outcome
Nishino M et al. Journal for ImmunoTherapy of Cancer 2014, 2:17.; Ribas A, et al. Clin Cancer Res 2009;15:7116–7118;
Wolchok JD et al. Clin Cancer Res. 2009;15(23):7412-20.
Tumour
immunotherapy
Immunotherapy-Hot topic
Ma…ma… che
c’è???
Target Therapy? ….Variabilita` Biologica!!
______________________________________________
Immunotherapy in Mesothelioma:
combinatorial approach
• Mesothelioma: lack of potent anti-tumor
T-cells and strong immunosuppressive tumor
microenvironment
• Induction of potent anti-tumor response by:
– Induction of tumor-specific T-cells : DC-immunotherapy
– Reduction of local immune suppression: CD40-agonist
• Hypothesis: combinatorial approach has a synergistic
effect on treatment outcome
Conclusions and future plans
CD40-agonist (in combination with DC-therapy):
• Enhanced mesothelioma survival
• Skewed monocytes to a pro-inflammatory, M1-like phenotype
• Increased CD8+ (and CD4+) T-cell proliferation and KLRG1+ CD8+ cells
Future plans:
Interim sacrifice of mice to investigate intra-tumoral leukocyte
populations
Validation of Ki67 and KLRG1 positive CD8 T-cells as potential
biomarkers for therapeutic success
Implementation of combinatorial approach in clinical trial
Ancona University Hospital
La prevenzione e la cura cominciano
dall’informazione
LA NUOVA ME: PINK DAY IN PINK ROOM
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